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A Matching-Adjusted Indirect Comparison of Upadacitinib Versus Tofacitinib in Adults with Moderate-to-Severe Rheumatoid Arthritis

INTRODUCTION: Upadacitinib and tofacitinib are Janus kinase inhibitors approved for moderate-to-severe rheumatoid arthritis (RA). In the absence of head-to-head trials comparing their effectiveness, this study assessed the efficacy of upadacitinib 15 mg once-daily monotherapy/combination therapy aga...

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Autores principales: Edwards, Christopher J., Sawant, Ruta, Garg, Vishvas, Du, Ella X., Friedman, Alan, Betts, Keith A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Healthcare 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7991064/
https://www.ncbi.nlm.nih.gov/pubmed/33244703
http://dx.doi.org/10.1007/s40744-020-00257-w
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author Edwards, Christopher J.
Sawant, Ruta
Garg, Vishvas
Du, Ella X.
Friedman, Alan
Betts, Keith A.
author_facet Edwards, Christopher J.
Sawant, Ruta
Garg, Vishvas
Du, Ella X.
Friedman, Alan
Betts, Keith A.
author_sort Edwards, Christopher J.
collection PubMed
description INTRODUCTION: Upadacitinib and tofacitinib are Janus kinase inhibitors approved for moderate-to-severe rheumatoid arthritis (RA). In the absence of head-to-head trials comparing their effectiveness, this study assessed the efficacy of upadacitinib 15 mg once-daily monotherapy/combination therapy against tofacitinib 5 mg twice-daily combination therapy among patients with RA using matching-adjusted indirect comparisons (MAICs). METHODS: The first of two MAICs used individual patient data (IPD) from the 14-week SELECT-MONOTHERAPY trial (upadacitinib [n = 217] vs. methotrexate [n = 216]) and published data from the ORAL Standard trial (tofacitinib + methotrexate [n = 204] vs. methotrexate [n = 108]). The second MAIC used IPD from the 26-week SELECT-COMPARE trial (upadacitinib + methotrexate [n = 647] vs. adalimumab + methotrexate [n = 324]) and published data from ORAL Strategy (tofacitinib + methotrexate [n = 376] vs. adalimumab + methotrexate [n = 386]). Data from patients in the upadacitinib trials were re-weighted based on age, sex, race, swollen joint count 66/28, tender joint count 68/28, C-reactive protein (CRP), and patients’ global assessments to match the patient characteristics in tofacitinib trials. After matching, ACR20/50/70 and clinical remission (SDAI[CRP] ≤ 3.3, CDAI ≤ 2.8, DAS28-ESR/CRP < 2.6) were compared for upadacitinib vs. tofacitinib + methotrexate at month 3 and upadacitinib + methotrexate vs. tofacitinib + methotrexate at months 3 and 6 using Wald tests. RESULTS: At month 3, upadacitinib monotherapy patients experienced significantly larger improvement in ACR70 compared to tofacitinib + methotrexate (mean difference in difference [DID]: 9.9%; p = 0.019), while upadacitinib + methotrexate was associated with higher ACR50 compared to tofacitinib + methotrexate (DID: 12.9%; p = 0.011). At month 6, upadacitinib + methotrexate patients experienced significantly larger improvement in SDAI/CDAI/DAS28-ESR clinical remission compared to tofacitinib + methotrexate, with DIDs of 9.1% (p = 0.011), 7.5% (p = 0.038), and 11.3% (p = 0.002), respectively. CONCLUSIONS: Compared to tofacitinib combination therapy, treatment with upadacitinib monotherapy and combination therapy were associated with improved outcomes at 3/6 months (monotherapy: ACR70; combination: ACR50, SDAI, CDAI, and DAS28-ESR remission). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s40744-020-00257-w) contains supplementary material, which is available to authorized users.
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spelling pubmed-79910642021-04-16 A Matching-Adjusted Indirect Comparison of Upadacitinib Versus Tofacitinib in Adults with Moderate-to-Severe Rheumatoid Arthritis Edwards, Christopher J. Sawant, Ruta Garg, Vishvas Du, Ella X. Friedman, Alan Betts, Keith A. Rheumatol Ther Original Research INTRODUCTION: Upadacitinib and tofacitinib are Janus kinase inhibitors approved for moderate-to-severe rheumatoid arthritis (RA). In the absence of head-to-head trials comparing their effectiveness, this study assessed the efficacy of upadacitinib 15 mg once-daily monotherapy/combination therapy against tofacitinib 5 mg twice-daily combination therapy among patients with RA using matching-adjusted indirect comparisons (MAICs). METHODS: The first of two MAICs used individual patient data (IPD) from the 14-week SELECT-MONOTHERAPY trial (upadacitinib [n = 217] vs. methotrexate [n = 216]) and published data from the ORAL Standard trial (tofacitinib + methotrexate [n = 204] vs. methotrexate [n = 108]). The second MAIC used IPD from the 26-week SELECT-COMPARE trial (upadacitinib + methotrexate [n = 647] vs. adalimumab + methotrexate [n = 324]) and published data from ORAL Strategy (tofacitinib + methotrexate [n = 376] vs. adalimumab + methotrexate [n = 386]). Data from patients in the upadacitinib trials were re-weighted based on age, sex, race, swollen joint count 66/28, tender joint count 68/28, C-reactive protein (CRP), and patients’ global assessments to match the patient characteristics in tofacitinib trials. After matching, ACR20/50/70 and clinical remission (SDAI[CRP] ≤ 3.3, CDAI ≤ 2.8, DAS28-ESR/CRP < 2.6) were compared for upadacitinib vs. tofacitinib + methotrexate at month 3 and upadacitinib + methotrexate vs. tofacitinib + methotrexate at months 3 and 6 using Wald tests. RESULTS: At month 3, upadacitinib monotherapy patients experienced significantly larger improvement in ACR70 compared to tofacitinib + methotrexate (mean difference in difference [DID]: 9.9%; p = 0.019), while upadacitinib + methotrexate was associated with higher ACR50 compared to tofacitinib + methotrexate (DID: 12.9%; p = 0.011). At month 6, upadacitinib + methotrexate patients experienced significantly larger improvement in SDAI/CDAI/DAS28-ESR clinical remission compared to tofacitinib + methotrexate, with DIDs of 9.1% (p = 0.011), 7.5% (p = 0.038), and 11.3% (p = 0.002), respectively. CONCLUSIONS: Compared to tofacitinib combination therapy, treatment with upadacitinib monotherapy and combination therapy were associated with improved outcomes at 3/6 months (monotherapy: ACR70; combination: ACR50, SDAI, CDAI, and DAS28-ESR remission). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s40744-020-00257-w) contains supplementary material, which is available to authorized users. Springer Healthcare 2020-11-26 /pmc/articles/PMC7991064/ /pubmed/33244703 http://dx.doi.org/10.1007/s40744-020-00257-w Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Original Research
Edwards, Christopher J.
Sawant, Ruta
Garg, Vishvas
Du, Ella X.
Friedman, Alan
Betts, Keith A.
A Matching-Adjusted Indirect Comparison of Upadacitinib Versus Tofacitinib in Adults with Moderate-to-Severe Rheumatoid Arthritis
title A Matching-Adjusted Indirect Comparison of Upadacitinib Versus Tofacitinib in Adults with Moderate-to-Severe Rheumatoid Arthritis
title_full A Matching-Adjusted Indirect Comparison of Upadacitinib Versus Tofacitinib in Adults with Moderate-to-Severe Rheumatoid Arthritis
title_fullStr A Matching-Adjusted Indirect Comparison of Upadacitinib Versus Tofacitinib in Adults with Moderate-to-Severe Rheumatoid Arthritis
title_full_unstemmed A Matching-Adjusted Indirect Comparison of Upadacitinib Versus Tofacitinib in Adults with Moderate-to-Severe Rheumatoid Arthritis
title_short A Matching-Adjusted Indirect Comparison of Upadacitinib Versus Tofacitinib in Adults with Moderate-to-Severe Rheumatoid Arthritis
title_sort matching-adjusted indirect comparison of upadacitinib versus tofacitinib in adults with moderate-to-severe rheumatoid arthritis
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7991064/
https://www.ncbi.nlm.nih.gov/pubmed/33244703
http://dx.doi.org/10.1007/s40744-020-00257-w
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