Miao Miao1,2, Yuhui Li1,2, Bo Huang1,2, Jiali Chen1,2, Yuebo Jin1,2, Miao Shao1,2, Xia Zhang1,2, Xiaolin Sun3,4, Jing He5,6, Zhanguo Li7,8,9. 1. Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing, 100044, China. 2. Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135), Beijing, China. 3. Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing, 100044, China. sunxiaolin_sxl@126.com. 4. Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135), Beijing, China. sunxiaolin_sxl@126.com. 5. Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing, 100044, China. hejing1105@126.com. 6. Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135), Beijing, China. hejing1105@126.com. 7. Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing, 100044, China. li99@bjmu.edu.cn. 8. Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135), Beijing, China. li99@bjmu.edu.cn. 9. Peking-Tsinghua Center for Life Sciences, Beijing, China. li99@bjmu.edu.cn.
Abstract
INTRODUCTION: Treatment of idiopathic inflammatory myopathies (IIMs) is challenging due to a lack of safe and efficacious medication. Low-dose interleukin-2 (IL-2) treatment emerges as a new option in active IIMs. This study aims to explore the clinical and immunological effects of low-dose IL-2 in patients with active IIMs. METHODS: Eighteen patients with active IIMs were enrolled and received 1 × 106 IU of IL-2 subcutaneously every other day for 12 weeks on top of standard care. The primary endpoint for the trial was change in percentage of regulatory T (Treg) cells in total CD4+ T cells at week 12. The secondary endpoints included the International Myositis Assessment and Clinical Studies (IMACS) definition of improvement (DOI), the 2016 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) myositis response criteria, safety, and steroid-sparing effect at weeks 12 and 24. RESULTS: With low-dose IL-2 treatment, 77.78% (14/18) patients achieved IMACS DOI and 83.33% (15/18) patients met the 2016 ACR/EULAR myositis response criteria at week 12. All individual core set measures (CSMs) including PhGA, PGA and HAQ-DI, muscle enzymes, MMT-8 and extramuscular activity were improved at week 12. The cutaneous dermatomyositis disease area and severity index activity score (CDASI-a) decreased significantly from 7 (4.5, 13) to 2 (0, 7) after IL-2 administration (P < 0.001). Proportion of Treg cells significantly increased with low-dose IL-2 treatment at week 12 (8.97% [5.77, 9.89%] vs. 15.2% [10.4, 17.3%], P = 0.009). There were no serious adverse events. CONCLUSIONS: Low-dose IL-2 was effective in active IIMs and well tolerated. The amelioration of disease activity may associate with promotion of Tregs. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT04062019.
INTRODUCTION: Treatment of idiopathic inflammatory myopathies (IIMs) is challenging due to a lack of safe and efficacious medication. Low-dose interleukin-2 (IL-2) treatment emerges as a new option in active IIMs. This study aims to explore the clinical and immunological effects of low-dose IL-2 in patients with active IIMs. METHODS: Eighteen patients with active IIMs were enrolled and received 1 × 106 IU of IL-2 subcutaneously every other day for 12 weeks on top of standard care. The primary endpoint for the trial was change in percentage of regulatory T (Treg) cells in total CD4+ T cells at week 12. The secondary endpoints included the International Myositis Assessment and Clinical Studies (IMACS) definition of improvement (DOI), the 2016 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) myositis response criteria, safety, and steroid-sparing effect at weeks 12 and 24. RESULTS: With low-dose IL-2 treatment, 77.78% (14/18) patients achieved IMACS DOI and 83.33% (15/18) patients met the 2016 ACR/EULAR myositis response criteria at week 12. All individual core set measures (CSMs) including PhGA, PGA and HAQ-DI, muscle enzymes, MMT-8 and extramuscular activity were improved at week 12. The cutaneous dermatomyositis disease area and severity index activity score (CDASI-a) decreased significantly from 7 (4.5, 13) to 2 (0, 7) after IL-2 administration (P < 0.001). Proportion of Treg cells significantly increased with low-dose IL-2 treatment at week 12 (8.97% [5.77, 9.89%] vs. 15.2% [10.4, 17.3%], P = 0.009). There were no serious adverse events. CONCLUSIONS: Low-dose IL-2 was effective in active IIMs and well tolerated. The amelioration of disease activity may associate with promotion of Tregs. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT04062019.
Entities:
Keywords:
Idiopathic inflammatory myopathies; Low-dose interleukin-2; Regulatory T cell
Authors: Lisa G Rider; Edward H Giannini; Michael Harris-Love; Galen Joe; David Isenberg; Clarissa Pilkington; Peter A Lachenbruch; Frederick W Miller Journal: J Rheumatol Date: 2003-03 Impact factor: 4.666