Abstract
Investigating the Effectiveness of Combined Tofacitinib and Cyclophosphamide Therapy in Rheumatoid Arthritis
Department of Clinical Medicine, The First Clinical Medical School, Guangzhou University of Traditional Chinese Medicine, 1Department of Rheumatology, The First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou, Guangdong Province 510000, China
Correspondence Address:
Tong Guan, Department of Rheumatology, The First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou, Guangdong Province 510000, China, E-mail: lsytgzya@163.com
Rheumatoid arthritis is a common inflammatory autoimmune disease; tofacitinib and cyclophosphamide have been discovered for the treatment of rheumatoid arthritis. However, single-agent therapy has limitations and combination therapy has become a research hotspot. Nevertheless, studies on the combination therapy of tofacitinib and cyclophosphamide have not been clearly reported. This study aims to investigate the efficacy of their combination therapy at both cellular and animal levels, providing new references for the combination therapy of rheumatoid arthritis. Tofacitinib and/or cyclophosphamide interventions were performed on human fibroblast-like synoviocytes rheumatoid arthritis cells to assess cell proliferation, apoptosis levels, and expression of inflammatory factors. In a rheumatoid arthritis animal model, joint tissue pathology, synovial tissue apoptosis levels, inflammatory factors, bone metabolism, Janus kinase signal transducer and activator of transcription signaling pathway and cluster of differentiation 4+ T-cell balance were evaluated. The combined treatment of tofacitinib and cyclophosphamide in human fibroblast-like synoviocytes rheumatoid arthritis cells resulted in decreased cell survival rate, reduced levels of interleukin-1, interleukin-6, tumor necrosis factor alpha, and B-cell lymphoma 2 messenger ribonucleic acid, increased B-cell lymphoma 2-associated protein X messenger ribonucleic acid levels, and decreased receptor activator of nuclear factor kappa-B ligand, receptor activator of nuclear factor kappa-B, C-terminal telopeptide of type I collagen, and N-terminal propeptide of type I procollagen levels in rheumatoid arthritis animal models. Additionally, there was a decrease in p-Janus kinase 2, and p-signal transducer and activator of transcription 3 protein expression levels, and alterations in the frequencies of T helper type 1, T helper type 2, T helper type 17, and regulatory T cells. Combining tofacitinib and cyclophosphamide can regulate cluster of differentiation 4+ T-cell balance, inhibit the p-Janus kinase 2/p-signal transducer and activator of transcription 3 pathway, reduce human fibroblast-like synoviocytes-rheumatoid arthritis cell proliferation and inflammation progression, and enhance synovial protection, leading to improved therapeutic efficacy compared to individual rheumatoid arthritis treatments.
Full-Text | PDF