Background: Tofacitinib (TOF), an oral JAK inhibitor, is approved for the treatment of rheumatoid arthritis (RA) either as monotherapy or in combination with background methotrexate (MTX). Despite the current evidence of efficacy from randomized controlled trials and open-label long-term extension studies, evidence of effectiveness and safety in real-world settings is limited, not only in Argentina but also in Latin America.

Objectives: To describe effectiveness, safety and persistence of TOF therapy in RA patients from public and private medical centers from Argentina. In addition, establish prognostic factors for clinical remission at 3 months and TOF monotherapy at 12 months.

Methods: A retrospective, observational and multicentre study was performed from an analysis of medical records of 10 medical centers. RA patients (ACR/EULAR, 2010) and age ≥ 18 years who had received or are under treatment with TOF until June 2020 were included. The data collection was done on a standard database that included baseline data and at 3, 6 and 12 months. Clinical remission was defined as DAS28-ESR < 2,6. Adverse events, treatment duration, TOF treatment persistence at last visit and discontinuation cause were assessed. Comparison to baseline values was performed using Wilcoxon sign for numerical variables and McNemar´s test for categorical variables. Treatment persistence was analyzed using Kaplan Meier´s technique. Multivariate analysis was performed using R software and its library packages (Lme4, Tidyverse and ggpubr). A p value < 0.05 was considered significant.

Results: A total of 167 patients were included (78.4% were female). At baseline, the median age was 53 years (IQR 43-63 years), median disease duration was 4 years (IQR 2-13 years). RF was positive in 85.6% of patients, ACPA in 80.8% and structural radiological damage was present in 71.8%. Previous use of MTX was 97%, leflunomide 74.8% and biologic therapy 42.5% (28.74% 1 biologic, 11.98% 2 biologics and 1.8% ≥ 3 biologics). TOF dose: 48% 11 mg/day and 52% 5 mg BID. A statistically significant difference was observed not only in disease activity (p<0.0001) but also in the requirement of MTX and PDN (p<0.0001) in the 12 months evaluated. Remission significantly increased from baseline to month 3 and to a much lesser extent to month 6 (p < 0.001). The mean duration of treatment with TOF was 20.10 ± 15.25 months. Treatment persistence was 93.84% at 3 months and 91.24% at 6 months. In those patient who achieved REM at month 3, a statistically significant differences in duration of RA (p 0.0002), structural radiological damage (p 0.011), basal disease activity (p 0.018) and prior treatment with biological therapy (p 0.017) was found when compared with patients who remained active. Furthermore, in univariate logistic regression analysis, 5 years or more of disease duration was associated with a 3 times higher risk of not achieving clinical remission at 3 months (odds ratio = 0.35, 95% CI = 0.15-0.83). In the multivariate logistic regression analysis, previous biological therapy was the only predictor associated with a decrease in the probability of clinical remission (p < 0.008). Adverse events were registered in 26 patients (herpes zoster, n = 9).

Conclusion: The effectiveness of TOF was observed not only in the clinical response achieved but also in the dose titration or withdrawal of MTX and PDN. The safety profile did not show any difference from long-term extension studies. At 12 months, 86.81% of the patients persisted with TOF therapy. We found prognostic factors associated with clinical remission at 3 months but those associated with monotherapy at 12 months could not be defined due to small number of patients analyzed that could have generated lack of statistical power, although more studies are required to confirm these assumptions.

Disclosure of Interests: Maria Del Rosario Maliandi: None declared, Yanina Silvia Malvano: None declared, Alejandra Cusa: None declared, María Julieta Gamba: None declared, Ramiro Gomez Speakers bureau: Abbvie, Novartis, Julio Got: None declared, Oscar Gut: None declared, Ursula Vanesa Paris: None declared, Maria Andrea Spinetto: None declared, Carolina Mariach: None declared, Alejandra Ines Abalo: None declared, Adrián Estevez Speakers bureau: Bristol-Meyer-Squibb, Jose Luis Velazco Zamora: None declared, Juan Pablo Vinicki: None declared