Induction of regulatory T cells and efficacy of low-dose interleukin-2 in systemic sclerosis : interventional open-label phase 1-phase 2a study
© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ..
BACKGROUND: Systemic sclerosis (SSc) is a chronic autoimmune disease, with impaired immune response, increased fibrosis and endothelial dysfunction. Regulatory T cells (Tregs), which are essential to control inflammation, tissue repair and autoimmunity, have a decreased frequency and impaired function in SSc patients. Low-dose interleukin-2 (IL-2LD) can expand and activate Tregs and has, therefore, a therapeutic potential in SSc.
OBJECTIVE: We aimed to assess the safety and biological efficacy of IL-2LD in patients with SSc.
METHODS: As part of the TRANSREG open-label phase IIa basket trial in multiple autoimmune diseases, we studied nine patients with SSc without severe organ involvement. Patients received 1 million international units (MIU)/day of IL-2 for 5 days, followed by fortnightly injections for 6 months. Laboratory and clinical evaluations were performed between baseline and month 6.
RESULTS: At day 8, the primary endpoint (Treg frequency) was reached with a 1.8±0.5-fold increase of Treg levels among CD4+ T lymphocytes (p=0.0015). There were no significant changes in effector T cells nor in B cells. IL-2LD was well tolerated, and no serious adverse events related to treatment occurred. There was a globally stable measurement in the modified Rodnan skin score and Valentini score at month 6. Disease activity and severity measures, the quality of life evaluated by EuroQL-5D-5L and pulmonary function test parameters remained stable during the study period.
CONCLUSION: IL-2LD at a dosage of 1 MIU/day safely and selectively activates and expands Tregs. Clinical signs remain stable during the study period. This opens the door to properly powered phase II efficacy trials investigating IL-2LD therapeutic efficacy in SSc.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:10 |
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| Enthalten in: |
RMD open - 10(2024), 2 vom: 04. Apr. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Barde, François [VerfasserIn] |
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| Links: |
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| Themen: |
Autoimmune Diseases |
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| Anmerkungen: |
Date Completed 08.04.2024 Date Revised 18.04.2024 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1136/rmdopen-2023-003500 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM370697561 |
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| 245 | 1 | 0 | |a Induction of regulatory T cells and efficacy of low-dose interleukin-2 in systemic sclerosis |b interventional open-label phase 1-phase 2a study |
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| 520 | |a © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. | ||
| 520 | |a BACKGROUND: Systemic sclerosis (SSc) is a chronic autoimmune disease, with impaired immune response, increased fibrosis and endothelial dysfunction. Regulatory T cells (Tregs), which are essential to control inflammation, tissue repair and autoimmunity, have a decreased frequency and impaired function in SSc patients. Low-dose interleukin-2 (IL-2LD) can expand and activate Tregs and has, therefore, a therapeutic potential in SSc | ||
| 520 | |a OBJECTIVE: We aimed to assess the safety and biological efficacy of IL-2LD in patients with SSc | ||
| 520 | |a METHODS: As part of the TRANSREG open-label phase IIa basket trial in multiple autoimmune diseases, we studied nine patients with SSc without severe organ involvement. Patients received 1 million international units (MIU)/day of IL-2 for 5 days, followed by fortnightly injections for 6 months. Laboratory and clinical evaluations were performed between baseline and month 6 | ||
| 520 | |a RESULTS: At day 8, the primary endpoint (Treg frequency) was reached with a 1.8±0.5-fold increase of Treg levels among CD4+ T lymphocytes (p=0.0015). There were no significant changes in effector T cells nor in B cells. IL-2LD was well tolerated, and no serious adverse events related to treatment occurred. There was a globally stable measurement in the modified Rodnan skin score and Valentini score at month 6. Disease activity and severity measures, the quality of life evaluated by EuroQL-5D-5L and pulmonary function test parameters remained stable during the study period | ||
| 520 | |a CONCLUSION: IL-2LD at a dosage of 1 MIU/day safely and selectively activates and expands Tregs. Clinical signs remain stable during the study period. This opens the door to properly powered phase II efficacy trials investigating IL-2LD therapeutic efficacy in SSc | ||
| 650 | 4 | |a Clinical Trial, Phase II | |
| 650 | 4 | |a Clinical Trial, Phase I | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Autoimmune Diseases | |
| 650 | 4 | |a Scleroderma, Systemic | |
| 650 | 4 | |a T-Lymphocyte subsets | |
| 650 | 7 | |a Interleukin-2 |2 NLM | |
| 700 | 1 | |a Lorenzon, Roberta |e verfasserin |4 aut | |
| 700 | 1 | |a Vicaut, Eric |e verfasserin |4 aut | |
| 700 | 1 | |a Rivière, Sébastien |e verfasserin |4 aut | |
| 700 | 1 | |a Cacoub, Patrice |e verfasserin |4 aut | |
| 700 | 1 | |a Cacciatore, Carlotta |e verfasserin |4 aut | |
| 700 | 1 | |a Rosenzwajg, Michelle |e verfasserin |4 aut | |
| 700 | 1 | |a Daguenel-Nguyen, Anne |e verfasserin |4 aut | |
| 700 | 1 | |a Fain, Olivier |e verfasserin |4 aut | |
| 700 | 1 | |a Klatzmann, David |e verfasserin |4 aut | |
| 700 | 1 | |a Mekinian, Arsène |e verfasserin |4 aut | |
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