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. 2024 Jun;11(3):563-582.
doi: 10.1007/s40744-024-00651-8. Epub 2024 Mar 11.

Real-World Effectiveness of Upadacitinib for Treatment of Rheumatoid Arthritis in Canadian Patients: Interim Results from the Prospective Observational CLOSE-UP Study

Louis Bessette  1 , Jonathan Chan  2 , Andrew Chow  3 , Larissa Lisnevskaia  4 , Nicolas Richard  5 , Pierre-Andre Fournier  6 , Dalinda Liazoghli  6 , Tanya Girard  6 , Derek Haaland  3
Affiliations

Real-World Effectiveness of Upadacitinib for Treatment of Rheumatoid Arthritis in Canadian Patients: Interim Results from the Prospective Observational CLOSE-UP Study

Louis Bessette et al. Rheumatol Ther. 2024 Jun.

Abstract

Introduction: Upadacitinib (UPA), a selective, reversible, oral Janus kinase (JAK)-1 inhibitor, was approved in 2019 in Canada for the treatment of adults with moderately to severely active rheumatoid arthritis (RA). This phase 4 prospective study aimed to characterise the effectiveness of UPA in the real-world population of patients with RA.

Methods: Adults with RA who initiated treatment with once daily UPA (15 mg) and enrolled in the Canadian Real-Life post-marketing Observational Study assessing the Effectiveness of UPadacitinib for treating rheumatoid arthritis (CLOSE-UP) and who completed a 6-month assessment as of 28 February 2023 were included. The primary endpoint of the CLOSE-UP study is the proportion of patients achieving a Disease Activity Score-28 Joint Count C-reactive protein (DAS28-CRP) < 2.6 at 6 months. Data was collected at routine visits. Data analysed and summarised descriptively for the overall interim population and for subgroups based on prior therapy included remission or low disease activity, patient-reported outcomes (PROs), and adverse events.

Results: A total of 392 patients were included in the interim analysis. Overall, 63.5% (191/301) of patients achieved a DAS28-CRP score < 2.6 at month 6, with similar rates observed for all subgroups analysed according to prior therapy including those with prior JAK inhibitor exposure (range 57.4-71.0%), and in patients who received UPA monotherapy (71.6% [48/67]). Early (month 3) and sustained improvements up to 6 months were observed for all PROs. The safety profile was consistent with previous reports.

Conclusion: Real-world improvements in disease activity and PROs in response to UPA treatment were consistent with clinical trial data across a range of Canadian patients with prior therapy exposure and with UPA monotherapy, with an overall favourable benefit-risk profile.

Trial registration: NCT04574492.

Keywords: Clinical trial; Janus kinase inhibitor; Phase 4; Real-world effectiveness; Rheumatoid arthritis; Upadacitinib.

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Conflict of interest statement

Louis Bessette reports consultancies, research grants, and speaker fees from BMS, Janssen, UCB, AbbVie, Pfizer, Sanofi, Lilly, and Novartis; research grants and speaker fees from Sandoz, Fresnius Kabi, Teva, Organon, and JAMP Pharma; and research grants from Gilead. Jonathan Chan reports consultancy and/or speaker fees and research grants from AbbVie, Pfizer, and UCB, and consultancy and/or speaker fees from Amgen, Celgene, Janssen, Novartis, Roche, Gilead, Eli Lilly, Merck, Fresenius Kabi, and Sandoz. Andrew Chow reports consultancies, research grants, and speaker fees from Abbvie, Amgen, AstraZeneca, BioJamp, Celltrion, Eli Lilly, Fresenius Kabi, Janssen, Novartis, Pfizer, UCB. Larissa Lisnevskaia has no conflicts to report. Nicolas Richard reports consultancies and/or speaker fees from Abbvie, Amgen, AstraZeneca, Eli Lilly, Janssen, Novartis, Pfizer and UCB. Pierre-Andre Fournier, Dalinda Liazoghli and Tanya Girard are employees of AbbVie Corporation. Derek Haaland reports honouraria from Abbvie, Amgen, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi-Genzyme, Takeda, UCB; advisory board or speakers’ bureau membership for Abbvie, Amgen, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen, Novartis, Pfizer, Roche, Sanofi Genzyme, Takeda; research funding from Abbvie, Adiga Life Sciences, Amgen, AstraZeneca, Bristol-Myers Squibb, Can-Fite Biopharma, Celgene, Eli Lilly, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, Regeneron, Sanofi-Genzyme, and UCB.

Figures

Fig. 1
Fig. 1
Proportion of patients in the overall interim analysis CLOSE-UP population and in subgroups of patients based on exposure to prior therapy achieving (i) DAS28-CRP < 2.6 (solid bars) or DAS28-CRP ≤ 3.2 (shaded bars), or remission (solid bars) or low disease activity (shaded bars) defined according to the (ii) CDAI, (iii) SDAI, and (iv) ACR-EULAR Boolean 2.0 criteria. Abbreviations: ACR-EULAR, American College of Rheumatology-European League Against Rheumatism; CDAI, Clinical Disease Activity Index; DAS28-CRP, Disease Activity Score-28 Joint Count C-reactive protein; SDAI, Simplified Disease Activity Index; tsDMARD, targeted synthetic disease-modifying antirheumatic drugs
Fig. 2
Fig. 2
Proportion of patients in the subgroups of patients treated with UPA monotherapy and a combination of UPA and csDMARDs achieving (i) DAS28-CRP < 2.6 (solid bars) or DAS28-CRP ≤ 3.2 (shaded bars), remission (solid bars) or low disease activity (shaded bars) defined according to the (ii) CDAI, (iii) SDAI, (iv) ACR-EULAR Boolean 2.0 criteria, or (v) a 50% reduction in pain score, or minimal clinically important difference in FACIT-F or HAQ-DI scores from baseline. Abbreviations: ACR-EULAR, American College of Rheumatology-European League Against Rheumatism; CDAI, Clinical Disease Activity Index; csDMARD, conventional synthetic disease-modifying antirheumatic drugs; DAS28-CRP, Disease Activity Score-28 Joint Count C-reactive protein; FACIT-F, Functional Assessment of Chronic Illness Therapy-Fatigue; HAQ-DI, Health Assessment Questionnaire-Disability Index; SDAI, Simplified Disease Activity Index; UPA, upadacitinib
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References

    1. Smolen JS, Landewe RBM, Bergstra SA, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update. Ann Rheum Dis. 2023;82(1):3–18. doi: 10.1136/ard-2022-223356. - DOI - PubMed
    1. Fraenkel L, Bathon JM, England BR, et al. 2021 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Care Res (Hoboken) 2021;73(7):924–939. doi: 10.1002/acr.24596. - DOI - PMC - PubMed
    1. Aletaha D, Smolen JS. Diagnosis and management of rheumatoid arthritis: a review. JAMA. 2018;320(13):1360–1372. doi: 10.1001/jama.2018.13103. - DOI - PubMed
    1. Scott IC, Ibrahim F, Panayi G, et al. The frequency of remission and low disease activity in patients with rheumatoid arthritis, and their ability to identify people with low disability and normal quality of life. Semin Arthritis Rheum. 2019;49(1):20–26. doi: 10.1016/j.semarthrit.2018.12.006. - DOI - PubMed
    1. 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. - DOI - PubMed

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