Rheumatoid arthritis (RA) is a chronic autoimmune disease affecting small joints, with a global prevalence of 0.5%-1.0% and 0.42% in China (around 5 million patients, mostly female and over 55). By 2050, RA patients worldwide are estimated to reach 31.7 million, an 80.2% increase from 2020. RA causes high disability rates, economic burdens, and can affect internal organs, leading to complications. Current treatments include csDMARDs (e.g., methotrexate, first-line but ineffective in half to two-thirds of patients), bDMARDs, tsDMARDs, NSAIDs, glucocorticoids, and traditional Chinese medicine.
Studies have explored bDMARDs' efficacy in csDMARDs-IR patients. Switching to or adding upadacitinib improves ACR20 response rates, with monotherapy showing higher safety. Filgotinib also showed superior efficacy over placebo in methotrexate-IR patients.
Ivarmacitinib, a novel JAK1 inhibitor, blocks cytokine signaling to reduce inflammation. A Phase II study (SHR0302-201) in moderate-to-severe RA patients showed ivarmacitinib 8 mg group had the highest ACR20 response rate (77.8%) after 12 weeks, with a dose-response relationship observed for ACR50/70 and DAS28-CRP improvements. TEAEs occurred in 73.9% of ivarmacitinib-treated patients, mostly infections, with upper respiratory tract infection being the most common.
A Phase III study (SHR0302-301) also in moderate-to-severe RA patients showed similar results after 24 weeks, with the ivarmacitinib 8 mg group again having the highest ACR20 response rate (75.1%). AEs were comparable between placebo and ivarmacitinib 4 mg groups but higher in the 8 mg group, with upper respiratory tract infection, anemia, and hyperlipidemia being common.
This project aims to investigate ivarmacitinib's therapeutic efficacy and safety in csDMARDs-IR RA patients, providing evidence for its use as a second-line treatment and exploring its effects at the single-cell sequencing and RNA-seq levels, offering new treatment options.