Long-Term Efficacy and Safety of Upadacitinib in Patients with Rheumatoid Arthritis: Final Results from the BALANCE-EXTEND Open-Label Extension Study.

Autor: Kivitz A; Altoona Center for Clinical Research, Duncansville, PA, USA. ajkivitz@yahoo.com., Wells AF; Aurora Rheumatology and Immunotherapy Center, Franklin, WI, USA., Vargas JI; Quantum Research, Puerto Varas, Los Lagos, Chile., Baraf HSB; The Center for Rheumatology and Bone Research, Wheaton, MD, USA.; The George Washington University, Washington, DC, USA., Rischmueller M; The Queen Elizabeth Hospital and Basil Hetzel Institute, Woodville South, SA, Australia.; Adelaide Medical School, University of Adelaide, Adelaide, SA, Australia., Klaff J; AbbVie Inc., North Chicago, IL, USA., Khan N; AbbVie Inc., North Chicago, IL, USA., Li Y; AbbVie Inc., North Chicago, IL, USA., Carter K; AbbVie Inc., North Chicago, IL, USA., Friedman A; AbbVie Inc., North Chicago, IL, USA., Durez P; Institut de Recherche Expérimentale et Cliniques Universitaires Saint-Luc, UCLouvain Saint-Luc, Brussels, Belgium.
Jazyk: angličtina
Zdroj: Rheumatology and therapy [Rheumatol Ther] 2023 Aug; Vol. 10 (4), pp. 901-915. Date of Electronic Publication: 2023 May 18.
DOI: 10.1007/s40744-023-00557-x
Abstrakt: Introduction: Upadacitinib (UPA) is an oral, selective Janus kinase inhibitor that has demonstrated favorable efficacy with an acceptable safety profile across a global, phase 3 program in rheumatoid arthritis (RA). This phase 2 open-label extension investigated the efficacy and safety of UPA through 6 years of treatment.
Methods: Patients from two phase 2b trials (BALANCE-1 and -2) enrolled in BALANCE-EXTEND (NCT02049138) and received open-label UPA 6 mg twice daily (BID). Dose increases to 12 mg BID were required for patients with < 20% improvement in swollen or tender joint counts at weeks 6 or 12 and permitted for those not achieving Clinical Disease Activity Index (CDAI) low disease activity (LDA; CDAI 2.8 to ≤ 10). Dose reduction to UPA 6 mg BID was permitted only for safety or tolerability reasons. After January 2017, the 6/12 mg BID doses were replaced by 15/30 mg once-daily extended-release equivalents. Efficacy and safety were monitored up to 6 years of UPA treatment; outcomes included rates of achievement of LDA or remission. Data were analyzed for patients who received the lower UPA dose throughout; titrated up to the higher UPA dose from weeks 6 or 12; or titrated to the higher UPA dose and back down.
Results: Overall, 493 patients entered BALANCE-EXTEND ('Never titrated', n = 306; 'Titrated up', n = 149; 'Titrated up and down', n = 38), and 223 patients (45%) completed the 6-year study. Total cumulative exposure was 1863 patient-years. Rates of LDA and remission were maintained through 6 years. Overall, 87%/70%/73% of patients in the 'Never titrated'/'Titrated up'/'Titrated up and down' groups achieved CDAI LDA at week 312, while the respective rates of Disease Activity Score 28 with C-reactive protein meeting LDA and remission criteria were 85%/69%/70% and 72%/46%/63%. Improvements in patient-reported outcomes were similar among the three groups. No new safety signals were identified.
Conclusions: In this open-label extension of two phase 2 studies, UPA demonstrated sustained efficacy and an acceptable safety profile through 6 years of treatment in patients who completed the study. These data support a favorable long-term benefit-risk profile of UPA in patients with RA.
Trial Registration: Trial registration number: NCT02049138.
(© 2023. The Author(s).)
Databáze: MEDLINE
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