Background: Filgotinib (FIL) is a selective JAK1 inhibitor with an affinity 30-fold higher than JAK2, approved to treat moderate to severe active rheumatoid arthritis (RA), in adults with inadequate response or intolerance to one or more disease-modifying antirheumatic drugs (DMARDs). Methods: We conducted a retrospective, multicentric study in order to evaluate efficacy and safety of FIL 200 mg daily therapy, after 3 and 6 months, in 120 patients affected by RA, managed in Tuscany and Umbria rheumatological centers. The following clinical records were analyzed: demographical data, smoking status, previous presence of comorbidities (Herpes zoster -HZ- infection, venous thromboembolism -VTE-, major adverse cardiovascular events -MACE-, cancer, diabetes, and hypertension), disease duration, presence of anti-citrullinated protein antibodies (ACPA), rheumatoid factor (RF), number of biological failures, and prior csDMARDs utilized. At baseline, and after 3 (T3) and 6 (T6) months of FIL therapy, we evaluated mean steroid dosage, csDMARDs intake, clinimetric indexes (DAS28, CDAI, HAQ, patient and doctor PGA, VAS), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and body mass index (BMI). Results: At baseline, the mean disease duration was 9.4 ± 7.5 years; the prevalence of previous HZ infection, VTE, MACE, and cancer was respectively 4.12%, 0%, 7.21%, and 0.83%, respectively. In total, 76.3% of patients failed one or more biologics (one biological failure, 20.6%; two biological failures, 27.8%; three biological failures, 16.5%; four biological failures, 10.3%; five biological failures, 1.1%). After 3 months of FIL therapy, all clinimetric index results significantly improved from baseline, as well as after 6 months. Also, ESR and CRP significatively decreased at T3 and T6. Two cases of HZ were recorded, while no new MACE, VTE, or cancer were recorded during the observation time. Conclusion: Despite the limitations of the retrospective study and of the observational period of only 6 months, real-life data on the treatment of RA patients with FIL demonstrate that this Jak inhibitor therapy is safe in terms of CV, VTE events, and occurrence of cancer, and is also effective in a population identified as “difficult to treat” due to failure of previous b-DMARD therapy.

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.

Background: We investigated how the non-medical switching (NMS) between Etanercept (ETN)/originator and SB4/biosimilar affects treatment efficacy in a rheumatic disease (RD) cohort, evaluating some laboratory parameters as loss of efficacy predictors after NMS. Methods: We enrolled 124 patients with RD (rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis): 79 switchers from ETN/originator to SB4 and 45 naïve patients receiving SB4 (first biological treatment). At baseline, 6 (T1), and 12 months (T2), clinical and laboratory parameters were evaluated. Results: In naïve patients, TNF-α significantly increased at T1 in responders (NR) and non-responders (NNR). TNF-α was lower in NNR than in NR at T1 and T2. In NR and NNR, drug levels (DL) increased between T1 and T2. However, DLs were lower in NNR than in NR at T1 and T2. TNF-α was higher in switcher responders (SR) than in non-responders (SNR) at T1 and T2. In SNR, DLs were higher at baseline than in SR, but they decreased significantly at T1 and T2. Conclusions: We observed a decrease in DL and TNF-α levels after NMS in SNR. Moreover, in naïve patients, DL and TNF-α levels were higher in NR than in NNR. Monitoring DL and TNF-α levels may represent a future precision medicine approach to predict loss of efficacy after NMS.

Full Papers; Authors: A. Damiani, F. Bartoli, G. Pacini, D. Carboni, S. Bellando Randone, G. Fiori, M. Matucci-Cerinic, S. Guiducci

The authors wish to make the following correction to this paper