Ab0724 Tofacitinib Drug Survival May Be Better in Obese TNF Inhibitor Resistant Ra Patients

Background: Patient with rheumatoid arthritis (RA) who are obese often have a reduced response to DMARD treatment, including TNF inhibitors (TNFi). Considering the different mechanisms of action it is important to evaluate the efficacy of tofacitinib in obese patients. Objectives: This study aims to explore the impact of obesity on the drug survival of tofacitinib in TNFi-resistant RA patients. Methods: This retrospective cohort study included RA patients treated with tofacitinib after at least one TNFi nonresponsiveness. Eligibility for inclusion in the study was determined based on the patient's history of treatment with at least one TNF inhibitor (TNFi) followed by subsequent administration of tofacitinib. Patients were categorized into obese (BMI ≥ 30 kg/m²) and non-obese (BMI < 30 kg/m²) groups. The primary outcome was drug survival, assessed using Kaplan-Meier and logistic regression analyses. Results: The study comprised 80 RA patients, with 31 (39%) classified as obese. At the 12-month mark, the drug survival rate for tofacitinib was higher in the obese group (81%) compared to the non-obese group (59%). The tofacitinib survival rate was 96.3% [92.2%-100.0%, 95% CI] at 90 days, 76.3% [67.5%-86.2%, 95% CI] at 180 days, and 68.7% [59.3%-79.7%, 95% CI] at 360 days in all patients. The tofacitinib survival rate was compared between both obese and non-obese TNFi-resistant RA groups. The one-year drug survival rate was higher in obese patients (81%) compared to non-obese patients (59%) (p=0.046). However, the estimated drug survival rates for tofacitinib did not show any statistical differences between obese and non-obese groups (Log rank p=0.12). Univariate and multivariate logistic regression analyses were conducted to assess the predictive abilities of sex, obesity, hypertension, diabetes mellitus, anti-CCP positivity on one year drug survival. The univariable analysis showed that obesity significantly increased the retention of tofacitinib treatment (HR: 2.87, 1.04-8.88 95% CI, p=0.05). However, in the multivariable analysis, obesity was not found to be associated with drug survival (HR: 2.83, 0.97-9.14 95% CI, p=0.065). Sex, hypertension, diabetes mellitus and anti-CCP positivity were not associated with drug survival in univariate and multivariate analysis. Conclusion: The findings indicate a potentially higher drug survival rate for tofacitinib among obese TNFi-resistant RA patients. Considering the possible underlying mechanism and better 12-months drug survival rate of TNFi-resistant RA patients with obesity on tofacitinib treatment, the use of tofacitinib can be pondered in treating obese RA patients with caution regarding other cardiovascular risk factors. In the light of these data, tofacitinib may be preferred in the obese RA patients because of its different pathway. However, the lack of statistical significance in multivariate analysis and the study's retrospective nature necessitate further research to validate these observations and guide personalized therapeutic strategies for this population. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests: None declared.