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Characterization and Changes of Lymphocyte Subsets in Baricitinib‐Treated Patients With Rheumatoid Arthritis: An Integrated Analysis
OBJECTIVE: Baricitinib is an orally administered inhibitor of JAK1 and JAK2 that has been shown to be effective in treating rheumatoid arthritis (RA). This study was undertaken to analyze changes in lymphocyte cell subsets during baricitinib treatment and to correlate these changes with clinical out...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6587754/ https://www.ncbi.nlm.nih.gov/pubmed/30058112 http://dx.doi.org/10.1002/art.40680 |
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author | Tanaka, Yoshiya McInnes, Iain B. Taylor, Peter C. Byers, Nicole L. Chen, Lei de Bono, Stephanie Issa, Maher Macias, William L. Rogai, Veronica Rooney, Terence P. Schlichting, Douglas E. Zuckerman, Steven H. Emery, Paul |
author_facet | Tanaka, Yoshiya McInnes, Iain B. Taylor, Peter C. Byers, Nicole L. Chen, Lei de Bono, Stephanie Issa, Maher Macias, William L. Rogai, Veronica Rooney, Terence P. Schlichting, Douglas E. Zuckerman, Steven H. Emery, Paul |
author_sort | Tanaka, Yoshiya |
collection | PubMed |
description | OBJECTIVE: Baricitinib is an orally administered inhibitor of JAK1 and JAK2 that has been shown to be effective in treating rheumatoid arthritis (RA). This study was undertaken to analyze changes in lymphocyte cell subsets during baricitinib treatment and to correlate these changes with clinical outcomes. METHODS: An integrated analysis was conducted by pooling data from 3 completed phase III trials comparing placebo with baricitinib treatment (RA‐BEAM, RA‐BUILD, and RA‐BEACON) and 1 ongoing long‐term extension study (RA‐BEYOND) in patients with active RA (n = 2,186). RESULTS: Baricitinib treatment was associated with an early transient increase in total lymphocyte count at week 4, which returned to baseline by week 12. Transient changes within normal reference ranges in T cells and subsets were observed with baricitinib treatment, up to week 104. B cells and relevant subpopulations increased after 4 weeks of baricitinib treatment, with no further increases noted through 104 weeks of treatment. Natural killer (NK) cells temporarily increased after 4 weeks of baricitinib treatment, before decreasing below baseline levels and then stabilizing over time. With baricitinib treatment, few correlations were observed between changes in lymphocyte subsets and clinical end points, and most correlations were also observed within the placebo group. A modest potential association between low NK cell numbers and treatment‐emergent infections was observed in the baricitinib 4 mg/day treatment group, but not for serious infections or herpes zoster. CONCLUSION: Overall, these findings demonstrate that changes in lymphocyte subsets were largely within normal reference ranges across the baricitinib phase III RA clinical program and were not associated with increased risk of serious infections. |
format | Online Article Text |
id | pubmed-6587754 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-65877542019-07-02 Characterization and Changes of Lymphocyte Subsets in Baricitinib‐Treated Patients With Rheumatoid Arthritis: An Integrated Analysis Tanaka, Yoshiya McInnes, Iain B. Taylor, Peter C. Byers, Nicole L. Chen, Lei de Bono, Stephanie Issa, Maher Macias, William L. Rogai, Veronica Rooney, Terence P. Schlichting, Douglas E. Zuckerman, Steven H. Emery, Paul Arthritis Rheumatol Rheumatoid Arthritis OBJECTIVE: Baricitinib is an orally administered inhibitor of JAK1 and JAK2 that has been shown to be effective in treating rheumatoid arthritis (RA). This study was undertaken to analyze changes in lymphocyte cell subsets during baricitinib treatment and to correlate these changes with clinical outcomes. METHODS: An integrated analysis was conducted by pooling data from 3 completed phase III trials comparing placebo with baricitinib treatment (RA‐BEAM, RA‐BUILD, and RA‐BEACON) and 1 ongoing long‐term extension study (RA‐BEYOND) in patients with active RA (n = 2,186). RESULTS: Baricitinib treatment was associated with an early transient increase in total lymphocyte count at week 4, which returned to baseline by week 12. Transient changes within normal reference ranges in T cells and subsets were observed with baricitinib treatment, up to week 104. B cells and relevant subpopulations increased after 4 weeks of baricitinib treatment, with no further increases noted through 104 weeks of treatment. Natural killer (NK) cells temporarily increased after 4 weeks of baricitinib treatment, before decreasing below baseline levels and then stabilizing over time. With baricitinib treatment, few correlations were observed between changes in lymphocyte subsets and clinical end points, and most correlations were also observed within the placebo group. A modest potential association between low NK cell numbers and treatment‐emergent infections was observed in the baricitinib 4 mg/day treatment group, but not for serious infections or herpes zoster. CONCLUSION: Overall, these findings demonstrate that changes in lymphocyte subsets were largely within normal reference ranges across the baricitinib phase III RA clinical program and were not associated with increased risk of serious infections. John Wiley and Sons Inc. 2018-10-22 2018-12 /pmc/articles/PMC6587754/ /pubmed/30058112 http://dx.doi.org/10.1002/art.40680 Text en © 2018 Eli Lilly and Company. Arthritis & Rheumatology published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Rheumatoid Arthritis Tanaka, Yoshiya McInnes, Iain B. Taylor, Peter C. Byers, Nicole L. Chen, Lei de Bono, Stephanie Issa, Maher Macias, William L. Rogai, Veronica Rooney, Terence P. Schlichting, Douglas E. Zuckerman, Steven H. Emery, Paul Characterization and Changes of Lymphocyte Subsets in Baricitinib‐Treated Patients With Rheumatoid Arthritis: An Integrated Analysis |
title | Characterization and Changes of Lymphocyte Subsets in Baricitinib‐Treated Patients With Rheumatoid Arthritis: An Integrated Analysis |
title_full | Characterization and Changes of Lymphocyte Subsets in Baricitinib‐Treated Patients With Rheumatoid Arthritis: An Integrated Analysis |
title_fullStr | Characterization and Changes of Lymphocyte Subsets in Baricitinib‐Treated Patients With Rheumatoid Arthritis: An Integrated Analysis |
title_full_unstemmed | Characterization and Changes of Lymphocyte Subsets in Baricitinib‐Treated Patients With Rheumatoid Arthritis: An Integrated Analysis |
title_short | Characterization and Changes of Lymphocyte Subsets in Baricitinib‐Treated Patients With Rheumatoid Arthritis: An Integrated Analysis |
title_sort | characterization and changes of lymphocyte subsets in baricitinib‐treated patients with rheumatoid arthritis: an integrated analysis |
topic | Rheumatoid Arthritis |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6587754/ https://www.ncbi.nlm.nih.gov/pubmed/30058112 http://dx.doi.org/10.1002/art.40680 |
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