A double-blind, placebo-controlled, randomized withdrawal trial of sarilumab for the treatment of glucocorticoid-dependent sarcoidosis
© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissionsoup.com..
OBJECTIVES: Effective steroid-sparing therapies for the treatment of sarcoidosis are lacking; interleukin-6 (IL-6) antagonists may reduce sarcoidosis disease activity. This study assessed the safety and efficacy of the IL-6 receptor antagonist, sarilumab, in subjects with glucocorticoid-dependent sarcoidosis.
METHODS: This phase II, double-blind, placebo-controlled, randomized withdrawal trial enrolled 15 subjects with biopsy-proven sarcoidosis at Stanford University from November 2019 to September 2022. In Period 1, subjects were treated with open-label sarilumab 200mg subcutaneously every two weeks for 16 weeks, with predefined tapering of prednisone. Subjects who completed Period 1 without a sarcoidosis flare entered Period 2 and were randomized to continue sarilumab or to receive matching placebo for 12 weeks. Endpoints included flare-free survival, as well as changes in pulmonary function tests, chest imaging, patient reported outcomes, and laboratory values.
RESULTS: Fifteen subjects were enrolled in the study (median age 57 years, 80% male, 73.3% White), and 10 subjects successfully completed Period 1. During Period 1, 4 of 15 subjects (26.7%) discontinued due to worsening of their sarcoidosis, and CT chest imaging worsened in 5 of 15 subjects (35.7%). During Period 2, 0 of 2 subjects in the sarilumab group and 1 of 8 subjects (12.5%) in the placebo group had a flare. Treatment with sarilumab 200 mg was generally well tolerated in subjects with sarcoidosis.
CONCLUSION: In this double-blind, placebo-controlled, randomized withdrawal trial, a meaningful signal for improvement in subjects with sarcoidosis treated with sarilumab was not observed. Given the small numbers in this study, no definitive conclusions can be drawn.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04008069.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2023 |
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| Enthalten in: |
Rheumatology (Oxford, England) - (2023) vom: 20. Juli |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Baker, Matthew C [VerfasserIn] |
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| Links: |
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| Themen: |
Granulomatous disease |
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| Anmerkungen: |
Date Revised 20.07.2023 published: Print-Electronic ClinicalTrials.gov: NCT04008069 Citation Status Publisher |
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| doi: |
10.1093/rheumatology/kead373 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM359720269 |
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| 100 | 1 | |a Baker, Matthew C |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a A double-blind, placebo-controlled, randomized withdrawal trial of sarilumab for the treatment of glucocorticoid-dependent sarcoidosis |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a ClinicalTrials.gov: NCT04008069 | ||
| 500 | |a Citation Status Publisher | ||
| 520 | |a © The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissionsoup.com. | ||
| 520 | |a OBJECTIVES: Effective steroid-sparing therapies for the treatment of sarcoidosis are lacking; interleukin-6 (IL-6) antagonists may reduce sarcoidosis disease activity. This study assessed the safety and efficacy of the IL-6 receptor antagonist, sarilumab, in subjects with glucocorticoid-dependent sarcoidosis | ||
| 520 | |a METHODS: This phase II, double-blind, placebo-controlled, randomized withdrawal trial enrolled 15 subjects with biopsy-proven sarcoidosis at Stanford University from November 2019 to September 2022. In Period 1, subjects were treated with open-label sarilumab 200mg subcutaneously every two weeks for 16 weeks, with predefined tapering of prednisone. Subjects who completed Period 1 without a sarcoidosis flare entered Period 2 and were randomized to continue sarilumab or to receive matching placebo for 12 weeks. Endpoints included flare-free survival, as well as changes in pulmonary function tests, chest imaging, patient reported outcomes, and laboratory values | ||
| 520 | |a RESULTS: Fifteen subjects were enrolled in the study (median age 57 years, 80% male, 73.3% White), and 10 subjects successfully completed Period 1. During Period 1, 4 of 15 subjects (26.7%) discontinued due to worsening of their sarcoidosis, and CT chest imaging worsened in 5 of 15 subjects (35.7%). During Period 2, 0 of 2 subjects in the sarilumab group and 1 of 8 subjects (12.5%) in the placebo group had a flare. Treatment with sarilumab 200 mg was generally well tolerated in subjects with sarcoidosis | ||
| 520 | |a CONCLUSION: In this double-blind, placebo-controlled, randomized withdrawal trial, a meaningful signal for improvement in subjects with sarcoidosis treated with sarilumab was not observed. Given the small numbers in this study, no definitive conclusions can be drawn | ||
| 520 | |a TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04008069 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Granulomatous disease | |
| 650 | 4 | |a Interleukin-6 | |
| 650 | 4 | |a Sarcoidosis | |
| 650 | 4 | |a Sarilumab | |
| 700 | 1 | |a Horomanski, Audra |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Yiwen |e verfasserin |4 aut | |
| 700 | 1 | |a Yuhan, Liu |e verfasserin |4 aut | |
| 700 | 1 | |a Parsafar, Shima |e verfasserin |4 aut | |
| 700 | 1 | |a Fairchild, Robert |e verfasserin |4 aut | |
| 700 | 1 | |a Mooney, Joshua J |e verfasserin |4 aut | |
| 700 | 1 | |a Raj, Rishi |e verfasserin |4 aut | |
| 700 | 1 | |a Witteles, Ronald |e verfasserin |4 aut | |
| 700 | 1 | |a Genovese, Mark C |e verfasserin |4 aut | |
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