Real-Life Comparison of Four JAK Inhibitors in Rheumatoid Arthritis (ELECTRA-i Study)

Area of Science:

• Rheumatology
• Pharmacology
• Immunology

Background:

• Limited real-world evidence exists for the efficacy and safety of JAK inhibitors (Tofacitinib, Baricitinib, Upadacitinib, Filgotinib) in rheumatoid arthritis (RA).
• This study addresses the need for comparative data on these treatments in a clinical setting.

Purpose of the Study:

• To evaluate the real-world efficacy and safety of four JAK inhibitors in patients with rheumatoid arthritis.
• To compare clinical and laboratory outcomes, including inflammatory markers and lipid metabolism, across different JAK inhibitors.

Main Methods:

• A cohort of 115 rheumatoid arthritis patients received Tofacitinib, Baricitinib, Upadacitinib, or Filgotinib.
• Clinical assessments (DAS28, CDAI, joint counts, VAS, HAQ) and laboratory parameters (calprotectin, TNFα, IL-6, suPAR, lipid profiles) were evaluated at 3, 6, and 12 months.
• Adverse events, including Venous Thrombotic Events (VTEs), Major Adverse Cardiovascular Events (MACEs), Herpes zoster, and Non-Melanoma Skin Cancer (NMSC), were recorded.

Main Results:

• All JAK inhibitors significantly reduced disease activity scores (DAS28, CDAI) and improved patient-reported outcomes.
• Statistically significant decreases in circulating calprotectin, TNFα, and IL-6 were observed for all treatments after 12 months.
• Differences in suPAR levels were noted for Filgotinib and Upadacitinib. The TC/HDL-C ratio varied significantly between Baricitinib, Filgotinib, Tofacitinib, and Upadacitinib, with Filgotinib showing no change in LDL-C/HDL-C ratio.
• Adverse events were infrequent, with VTEs/MACEs (1%) for Baricitinib, Herpes zoster (1%) for Filgotinib and Tofacitinib, and NMSC (1%) for Upadacitinib.

Conclusions:

• Real-world data confirm the efficacy of JAK inhibitors in rheumatoid arthritis, with comparable clinical responses across agents.
• Distinct effects on specific laboratory parameters, such as suPAR and lipid metabolism (atherogenic index), were observed among the JAK inhibitors.
• The safety profiles were generally favorable, with low incidences of major adverse events, though specific risks like VTEs, Herpes zoster, and NMSC were noted.