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Real-Life Comparison of Four JAK Inhibitors in Rheumatoid Arthritis (ELECTRA-i Study)
Maurizio Benucci1, Francesca Li Gobbi1, Arianna Damiani2
1Rheumatology Unit, S. Giovanni di Dio Hospital, Azienda USL-Toscana Centro, 50143 Florence, Italy.
Insights
Real-world data shows JAK inhibitors (Tofacitinib, Baricitinib, Upadacitinib, Filgotinib) effectively treat rheumatoid arthritis with varying impacts on lab markers and lipid metabolism. Adverse events were generally low across treatments.
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.
Abstract:
Background: Real-world evidence of the efficacy and adverse events of JAK inhibitor treatment (Tofacitinib, Baricitinib, Upadacitinib, and Filgotinib) in rheumatoid arthritis is still limited. Methods: We studied 115 patients from the Rheumatology Unit of S. Giovanni di Dio Hospital affected by D2T-RA, according to the 2010 EULAR criteria. Out of the 115 patients, 17 had been treated with Baricitinib 8 mg/daily, 32 with Filgotinib 200 mg/daily, 21 with Tofacitinib 10 mg/daily, and 45 with Upadacitinib 15 mg/daily. We evaluated the clinical response after 3, 6, and 12 months of treatment and the follow-up from September 2022 to September 2023. All patients were evaluated according to the number of tender joints (NTJs), number of swollen joints (NSJs), visual analog scale (VAS), global assessment (GA), health assessment questionnaire (HAQ), Disease Activity Score (DAS28), and CDAI. Furthermore, laboratory parameters of efficacy and tolerability were evaluated. Results: All treatments demonstrated a statistically significant decrease in the DAS28 and CDAI scores, tender and swollen joint counts, VAS, HAQ, and patient global assessment (PGA) after 3, 6, and 12 months of treatment. All treatments showed similar behavior, and statistically significant decreases in circulating calprotectin, TNFα, and IL-6 were observed for all drugs after 12 months of treatment. In addition, soluble urokinase plasminogen activator receptor (suPAR) values showed significant differences at baseline and after 12 months of treatment for Filgotinib: 4.87 ± 4.53 vs. 3.61 ± 0.9 (0.009) and Upadacitinib: 6.64 ± 7.12 vs. 4.06 ± 3.61 (0.0003), while no statistically significant differences were found for Baricitinib: 3.4 ± 0.1 vs. 3.78 ± 0.1 and Tofacitinib: 3.95 ± 1.77 vs. 2.58 ± 0.1. The TC/HDL-C ratio (atherogenic index) showed significant differences when comparing Baricitinib vs. Filgotinib (0.0012), Filgotinib vs. Tofacitinib (0.0095), and Filgotinib vs. Upadacitinib (0.0001); furthermore, the LDL-C/HDL-C ratio in the Filgotinib group did not change (2.37 ± 0.45 vs. 2.35 ± 2.13 (NS)) after 12 months of treatment. Venous Thrombotic Events (VTEs) and major adverse cardiovascular events (MACEs) accounted for 1% of adverse events after treatment with Baricitinib. Herpes zoster reactivation accounted for 1% of adverse events after treatment with Filgotinib and Tofacitinib, while non-melanoma skin cancer (NMSC) accounted for 1% of adverse events after Upadacitinib treatment. Conclusions: Our real-world data from patients with RA show differences in some laboratory parameters and in the impact of lipid metabolism in JAK inhibitor treatment.
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