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Low-Dose Sirolimus Immunoregulation Therapy in Patients with Active Rheumatoid Arthritis: A 24-Week Follow-Up of the Randomized, Open-Label, Parallel-Controlled Trial.
- Source :
-
Journal of immunology research [J Immunol Res] 2019 Nov 03; Vol. 2019, pp. 7684352. Date of Electronic Publication: 2019 Nov 03 (Print Publication: 2019). - Publication Year :
- 2019
-
Abstract
- Background: We have reported previously the insufficient absolute number or functional defects of regulatory T cells (Tregs) in patients with rheumatoid arthritis (RA), challenging conventional unspecific immunosuppressive therapy. Sirolimus, a mTOR inhibitor, is reported to allow growth of functional Tregs; here, we investigated the efficacy of low-dose sirolimus combined with conventional immunosuppressants (sirolimus immunoregulation therapy) for RA treatment with lower side effects and better tolerance.<br />Methods: In this nonblinded and parallel-group trial, we randomly assigned 62 patients to receive conventional glucocorticoids and immunosuppressants with or without sirolimus at a dosage of 0.5âmg on alternate days for 24 weeks in a 2â:â1 ratio. The demographic features, clinical manifestations, and laboratory indicators including peripheral blood lymphocyte subgroups and CD4 <superscript>+</superscript> T subsets were compared before and after the treatment.<br />Results: Finally, 37 patients in the sirolimus group and 18 in the conventional treated group completed the 6-month study. By 24 weeks, the patients with sirolimus experienced significant reduction in disease activity indicators including DAS28, ESR, and the number of tender joints and swollen joints ( p < 0.001). Notably, they had a higher level of Tregs as compared with those with conventional therapy alone ( p < 0.05), indicating that sirolimus could partly restore the reduced Tregs. Concomitantly, their usage of immunosuppressants for controlling disease activity was decreased as compared with the conventional group with no difference in blood routine, and liver and renal functions both before and after the treatment of sirolimus and between the two groups ( p > 0.05).<br />Conclusions: Low-dose sirolimus immunoregulatory therapy selectively upregulated Tregs and partly replaced the usage of immunosuppressants to control disease activity without overtreatment and evaluable side effect. Further study is required using a large sample of RA patients treated with sirolimus for a longer period. This trial is registered at the Chinese Clinical Trial Registry (http://www.chictr.org.cn/showproj.aspx?proj=17245).<br />Competing Interests: The authors declare that they have no competing interests.<br /> (Copyright © 2019 Hong-Yan Wen et al.)
- Subjects :
- Adult
Arthritis, Rheumatoid diagnosis
Biomarkers
Female
Follow-Up Studies
Humans
Male
Middle Aged
Severity of Illness Index
T-Lymphocyte Subsets drug effects
T-Lymphocyte Subsets immunology
T-Lymphocyte Subsets metabolism
T-Lymphocytes, Regulatory drug effects
T-Lymphocytes, Regulatory immunology
T-Lymphocytes, Regulatory metabolism
Treatment Outcome
Arthritis, Rheumatoid drug therapy
Arthritis, Rheumatoid immunology
Immunomodulation drug effects
Immunosuppressive Agents administration & dosage
Sirolimus administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 2314-7156
- Volume :
- 2019
- Database :
- MEDLINE
- Journal :
- Journal of immunology research
- Publication Type :
- Academic Journal
- Accession number :
- 31781682
- Full Text :
- https://doi.org/10.1155/2019/7684352