A Systematic Review and Meta-analysis of the Efficacy and Safety of Iguratimod in the Treatment of Inflammatory Arthritis and Degenerative Arthritis

Overview

Journal Front Pharmacol

Date 2024 Oct 25

PMID 39449973

Authors

Zhiyong Long

Liuting Zeng

Kailin Yang

Junpeng Chen

Yanfang Luo

Charles C Dai

Qi He

Ying Deng

Anqi Ge

Xiaofei Zhu

Wensa Hao

Lingyun Sun

Affiliations

Soon will be listed here.

Abstract

Objective: To assess the efficacy and safety of iguratimod (IGU) in the treatment of inflammatory arthritis and degenerative arthritis.

Methods: Initially, randomized controlled trials (RCTs) on using IGU in treating inflammatory arthritis and degenerative arthritis were systematically gathered from various databases up to February 2024. Subsequently, two researchers independently screened the literature, extracted data, assessed the risk of bias in included studies, and conducted a meta-analysis using RevMan 5.4 software.

Results: Fifty-four RCTs involving three inflammatory arthritis were included, including ankylosing spondylitis (AS), osteoarthritis (OA), and rheumatoid arthritis (RA). For AS, the meta-analysis results showed that IGU may decrease BASDAI (SMD -1.68 [-2.32, -1.03], < 0.00001) and BASFI (WMD -1.29 [-1.47, -1.11], < 0.00001); IGU may also decrease inflammatory factor [ESR: (WMD -10.33 [-14.96, -5.70], < 0.0001); CRP: (WMD -10.11 [-14.55, -5.66], < 0.00001); TNF-α: (WMD -6.22 [-7.97, -4.47], < 0.00001)]. For OA, the meta-analysis results showed that IGU may decrease VAS (WMD -2.20 [-2.38, -2.01], < 0.00001) and WOMAC (WMD -7.27 [-12.31, -2.24], = 0.005); IGU may also decrease IL-6 (WMD -8.72 [-10.00, -7.45], < 0.00001). For RA, the meta-analysis results showed that IGU may improve RA remission rate [ACR20: (RR 1.18 [1.02, 1.35], = 0.02); ACR50: (RR 1.32 [1.05, 1.64], = 0.02); ACR70: (RR 1.44 [1.02, 2.04], = 0.04)] and decrease DAS28 (WMD -0.92 [-1.20, -0.63], < 0.00001); IGU may also decrease inflammatory factors [CRP: (SMD -1.36 [-1.75, -0.96], < 0.00001); ESR: (WMD -9.09 [-11.80, -6.38], < 0.00001); RF: (SMD -1.21 [-1.69, -0.73], < 0.00001)]. Regarding safety, adding IGU will not increase the incidence of adverse events.

Conclusion: IGU might emerge as a promising and secure therapeutic modality for addressing AS, OA, and RA.

Systematic Review Registration: Identifier PROSPERO: CRD42021289249.

References

Wang X, Ma C, Li P, Zhao F, Bi L . Effects of iguratimod on the levels of circulating regulators of bone remodeling and bone remodeling markers in patients with rheumatoid arthritis. Clin Rheumatol. 2017; 36(6):1369-1377. DOI: 10.1007/s10067-017-3668-8. View

Minnig M, Golightly Y, Nelson A . Epidemiology of osteoarthritis: literature update 2022-2023. Curr Opin Rheumatol. 2024; 36(2):108-112. PMC: 10965245. DOI: 10.1097/BOR.0000000000000985. View

Miura T, Etani Y, Noguchi T, Hirao M, Takami K, Goshima A . Iguratimod suppresses sclerostin and receptor activator of NF-κB ligand production via the extracellular signal-regulated kinase/early growth response protein 1/tumor necrosis factor alpha pathway in osteocytes and ameliorates disuse osteoporosis in.... Bone. 2024; 181:117026. DOI: 10.1016/j.bone.2024.117026. View

Liu Z, Cai M, Ke H, Deng H, Ye W, Wang T . Fibroblast Insights into the Pathogenesis of Ankylosing Spondylitis. J Inflamm Res. 2023; 16:6301-6317. PMC: 10750494. DOI: 10.2147/JIR.S439604. View

Lau C . Burden of rheumatoid arthritis and forecasted prevalence to 2050. Lancet Rheumatol. 2024; 5(10):e567-e568. DOI: 10.1016/S2665-9913(23)00240-0. View

Knights A, Redding S, Maerz T . Inflammation in osteoarthritis: the latest progress and ongoing challenges. Curr Opin Rheumatol. 2023; 35(2):128-134. PMC: 10821795. DOI: 10.1097/BOR.0000000000000923. View

Gravallese E, Firestein G . Rheumatoid Arthritis - Common Origins, Divergent Mechanisms. N Engl J Med. 2023; 388(6):529-542. DOI: 10.1056/NEJMra2103726. View

Lu L, Teng J, Bao C, Han X, Sun L, Xu J . Safety and efficacy of T-614 in the treatment of patients with active rheumatoid arthritis: a double blind, randomized, placebo-controlled and multicenter trial. Chin Med J (Engl). 2008; 121(7):615-9. View

Zeng L, He Q, Yang K, Hao W, Yu G, Chen H . A Systematic Review and Meta-Analysis of 19 Randomized Controlled Trials of Iguratimod Combined With Other Therapies for Sjogren's Syndrome. Front Immunol. 2022; 13:924730. PMC: 9367640. DOI: 10.3389/fimmu.2022.924730. View

10.

Sarzi-Puttini P, Zen M, Arru F, Giorgi V, Choy E . Residual pain in rheumatoid arthritis: Is it a real problem?. Autoimmun Rev. 2023; 22(11):103423. DOI: 10.1016/j.autrev.2023.103423. View

11.

Yoshioka Y, Takahashi N, Kaneko A, Hirano Y, Kanayama Y, Kanda H . Disease activity early in treatment as a predictor of future low disease activity in RA patients treated with iguratimod. Mod Rheumatol. 2015; 26(2):169-74. DOI: 10.3109/14397595.2015.1069475. View

12.

Zhou S, Zhao G, Chen R, Li Y, Huang J, Kuang L . Lymphatic vessels: roles and potential therapeutic intervention in rheumatoid arthritis and osteoarthritis. Theranostics. 2024; 14(1):265-282. PMC: 10750203. DOI: 10.7150/thno.90940. View

13.

Harmalkar D, Sivaraman A, Nada H, Lee J, Kang H, Choi Y . Natural products as IL-6 inhibitors for inflammatory diseases: Synthetic and SAR perspective. Med Res Rev. 2024; 44(4):1683-1726. DOI: 10.1002/med.22022. View

14.

Luo Q, Sun Y, Liu W, Qian C, Jin B, Tao F . A novel disease-modifying antirheumatic drug, iguratimod, ameliorates murine arthritis by blocking IL-17 signaling, distinct from methotrexate and leflunomide. J Immunol. 2013; 191(10):4969-78. DOI: 10.4049/jimmunol.1300832. View

15.

Juma S, Liao J, Huang Y, Vlashi R, Wang Q, Wu B . Osteoarthritis versus psoriasis arthritis: Physiopathology, cellular signaling, and therapeutic strategies. Genes Dis. 2024; 11(3):100986. PMC: 10825447. DOI: 10.1016/j.gendis.2023.04.021. View

16.

Katz J, Bartels C . Multimorbidity in Rheumatoid Arthritis: Literature Review and Future Directions. Curr Rheumatol Rep. 2023; 26(1):24-35. PMC: 11463754. DOI: 10.1007/s11926-023-01121-w. View

17.

Sun L, Tao J, Han Z, Chen H, Huang Z, Wang Z . Efficacy of iguratimod on mineral and bone disorders after kidney transplantation: a preliminary study. Ren Fail. 2023; 45(2):2256418. PMC: 11001337. DOI: 10.1080/0886022X.2023.2256418. View

18.

Duan X, Zhang X, Mao S, Shang J, Shi X . Efficacy and safety evaluation of a combination of iguratimod and methotrexate therapy for active rheumatoid arthritis patients: a randomized controlled trial. Clin Rheumatol. 2015; 34(9):1513-9. DOI: 10.1007/s10067-015-2999-6. View

19.

Xu B, Xing R, Huang Z, Yin S, Li X, Zhang L . Excessive mechanical stress induces chondrocyte apoptosis through TRPV4 in an anterior cruciate ligament-transected rat osteoarthritis model. Life Sci. 2019; 228:158-166. DOI: 10.1016/j.lfs.2019.05.003. View

20.

van de Sande M, Elewaut D . Pathophysiology and immunolgical basis of axial spondyloarthritis. Best Pract Res Clin Rheumatol. 2023; 37(3):101897. DOI: 10.1016/j.berh.2023.101897. View