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Tapering and discontinuation of glucocorticoids in patients with rheumatoid arthritis treated with tofacitinib

Although the rapid onset of effect of glucocorticoids (GCs) allows rapid control of rheumatoid arthritis (RA) symptoms, their chronic use may be associated with several adverse events. The 2022 update of EUALR recommendations for the management of patients with RA suggests to reduce and discontinue...

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Autores principales: Spinelli, Francesca Romana, Garufi, Cristina, Mancuso, Silvia, Ceccarelli, Fulvia, Truglia, Simona, Conti, Fabrizio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10511736/
https://www.ncbi.nlm.nih.gov/pubmed/37730835
http://dx.doi.org/10.1038/s41598-023-42371-z
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author Spinelli, Francesca Romana
Garufi, Cristina
Mancuso, Silvia
Ceccarelli, Fulvia
Truglia, Simona
Conti, Fabrizio
author_facet Spinelli, Francesca Romana
Garufi, Cristina
Mancuso, Silvia
Ceccarelli, Fulvia
Truglia, Simona
Conti, Fabrizio
author_sort Spinelli, Francesca Romana
collection PubMed
description Although the rapid onset of effect of glucocorticoids (GCs) allows rapid control of rheumatoid arthritis (RA) symptoms, their chronic use may be associated with several adverse events. The 2022 update of EUALR recommendations for the management of patients with RA suggests to reduce and discontinue oral GCs as quickly as possible. Considering GCs as a "bridging therapy" to promptly reduce symptoms and control inflammation, fast-acting drugs such as tofacitinib could allow faster and safer tapering of GCs. The purpose of this pilot study was to evaluate the steroid-sparing effect of adding tofacitinib in patients with RA inadequately responsive to methotrexate taking concomitant GCs. In this open-label pilot study, we enrolled patients with moderate to severe RA on a stable dose of prednisone (5–12.5 mg/day) who started treatment with tofacitinib. After 1 month, in patients who achieved at least a moderate EULAR response (decrease of > 1.2 in DAS28_CRP), GCs was tapered according to a predetermined schedule until complete discontinuation at week 12. Disease activity was assessed after 4, 12, 24 and 48 weeks of treatment. The primary endpoint was the percentage of patients discontinuing GCs after 12 weeks of tofacitinib treatment. We enrolled 30 patients (26 F: 4 M, mean age 60 ± 13 years, mean disease duration 13.2 ± 7.8 years). The primary endpoint was achieved: 9 patients (30%) discontinued GCs at week-12. At week-24, other 12 patients (46%) withdrew GCs. The median prednisone dose decreased from 5 mg/day (interquartile range 5–10 mg) to 2.5 (0–5) mg/day at week 12 and 48 (p < 0.00001 vs baseline). At week 48, 12 out of 30 patients (40%) had discontinued prednisone. The percentage of patients achieving remission or low disease activity increased throughout the follow-up without any difference between patients who discontinued or not the GC. In this cohort of long-standing RA patients treated with tofacitinib, the discontinuation of glucocorticoids was achievable in up to 30% of patients. These results should encourage rheumatologists to consider GCs tapering and discontinuation of GCs, as suggested by the 2022 EULAR recommendations, an achievable goal.
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spelling pubmed-105117362023-09-22 Tapering and discontinuation of glucocorticoids in patients with rheumatoid arthritis treated with tofacitinib Spinelli, Francesca Romana Garufi, Cristina Mancuso, Silvia Ceccarelli, Fulvia Truglia, Simona Conti, Fabrizio Sci Rep Article Although the rapid onset of effect of glucocorticoids (GCs) allows rapid control of rheumatoid arthritis (RA) symptoms, their chronic use may be associated with several adverse events. The 2022 update of EUALR recommendations for the management of patients with RA suggests to reduce and discontinue oral GCs as quickly as possible. Considering GCs as a "bridging therapy" to promptly reduce symptoms and control inflammation, fast-acting drugs such as tofacitinib could allow faster and safer tapering of GCs. The purpose of this pilot study was to evaluate the steroid-sparing effect of adding tofacitinib in patients with RA inadequately responsive to methotrexate taking concomitant GCs. In this open-label pilot study, we enrolled patients with moderate to severe RA on a stable dose of prednisone (5–12.5 mg/day) who started treatment with tofacitinib. After 1 month, in patients who achieved at least a moderate EULAR response (decrease of > 1.2 in DAS28_CRP), GCs was tapered according to a predetermined schedule until complete discontinuation at week 12. Disease activity was assessed after 4, 12, 24 and 48 weeks of treatment. The primary endpoint was the percentage of patients discontinuing GCs after 12 weeks of tofacitinib treatment. We enrolled 30 patients (26 F: 4 M, mean age 60 ± 13 years, mean disease duration 13.2 ± 7.8 years). The primary endpoint was achieved: 9 patients (30%) discontinued GCs at week-12. At week-24, other 12 patients (46%) withdrew GCs. The median prednisone dose decreased from 5 mg/day (interquartile range 5–10 mg) to 2.5 (0–5) mg/day at week 12 and 48 (p < 0.00001 vs baseline). At week 48, 12 out of 30 patients (40%) had discontinued prednisone. The percentage of patients achieving remission or low disease activity increased throughout the follow-up without any difference between patients who discontinued or not the GC. In this cohort of long-standing RA patients treated with tofacitinib, the discontinuation of glucocorticoids was achievable in up to 30% of patients. These results should encourage rheumatologists to consider GCs tapering and discontinuation of GCs, as suggested by the 2022 EULAR recommendations, an achievable goal. Nature Publishing Group UK 2023-09-20 /pmc/articles/PMC10511736/ /pubmed/37730835 http://dx.doi.org/10.1038/s41598-023-42371-z Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits 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/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Spinelli, Francesca Romana
Garufi, Cristina
Mancuso, Silvia
Ceccarelli, Fulvia
Truglia, Simona
Conti, Fabrizio
Tapering and discontinuation of glucocorticoids in patients with rheumatoid arthritis treated with tofacitinib
title Tapering and discontinuation of glucocorticoids in patients with rheumatoid arthritis treated with tofacitinib
title_full Tapering and discontinuation of glucocorticoids in patients with rheumatoid arthritis treated with tofacitinib
title_fullStr Tapering and discontinuation of glucocorticoids in patients with rheumatoid arthritis treated with tofacitinib
title_full_unstemmed Tapering and discontinuation of glucocorticoids in patients with rheumatoid arthritis treated with tofacitinib
title_short Tapering and discontinuation of glucocorticoids in patients with rheumatoid arthritis treated with tofacitinib
title_sort tapering and discontinuation of glucocorticoids in patients with rheumatoid arthritis treated with tofacitinib
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10511736/
https://www.ncbi.nlm.nih.gov/pubmed/37730835
http://dx.doi.org/10.1038/s41598-023-42371-z
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