AB0344 FACTORS WHICH CONTRIBUTE PERSISTENCY AND OPTIMAL USE OF TOFACITINIB; LESSONS FROM LONG TERM DAILY CLINICAL USE OF TOFACITINIB
Authors: N. Iwamoto, T. Aramaki, K. Ichinose, Y. Ueki, A. Kawakami
Journal: Annals of the Rheumatic Diseases (2020)

Background: Recently, tofacitinib treatment in rheumatoid arthritis (RA) is thought to be not inferior to other biologic disease-modifying antirheumatic drugs (bDMARDS) such as TNF-inhibitor. However, approval of tofacitinib for treatment with RA is relatively recent as compared to other bDMARDs, therefore until now, little knowledge about long term efficacy and safety of tofacitinib in real-world settings or about which patients should be initiated tofacitinib are available. Thus, we need evidence from real-world setting for optimal use of tofacitinib. Objectives: To investigate the efficacy and safety of tofacitinib and to identify factors which contribute persistency and efficacy of tofacitinib treatment during 2 years. Methods: 148 patients, for whom tofacitinib was initiated until January 2018 were enrolled. All patients received 5 mg of tofacitinib twice daily and were followed for 2 years. Clinical disease activity indicated by disease activity score (DAS)28-ESR as well as adverse events (AEs) were evaluated. Statistical analysis was performed to determine which baseline variables influenced the persistency and efficacy of tofacitinib. Results: 92 patients (62.2 %) continued tofacitinib for 2 years. Clinical disease activity rapidly and significantly decreased, and this efficacy continued throughout the 2 years: i.e., DAS28-ESR decreased from 5.13 ± 1.42 at baseline to 4.02 ± 1.11 at 4 weeks and 3.91 ± 1.32 at 2 years (P&lt;0.0001, vs. baseline). 55 AEs including 22 herpes zoster infection occurred during tofacitinib treatment. 27 patients discontinued tofacitinib due to lack of efficacy. Multivariable logistic analysis showed that the number of bDMARDs previously used and age were associated with discontinuation of tofacitinib treatment due to lack of efficacy(table 1). Another set of multivariable logistic analysis revealed that lower disease activity at baseline contributed the achievement of DAS-low disease activity(odds ratio= 1.56, 95% confidence interval: 0.48-0.85). In the concomitant use of MTX or without MTX, the Δ values of DAS28-ESR from baseline to 24 months were -1.62, -1.13, respectively(P=0.12). And, the efficacy of patients after switching from tocilizumab(TCZ), which also inhibit IL-6 as same as JAK inhibitor, were not inferior as compared to non-switching from TCZ (Δ DAS28-ESR;-1.07, -1.61, respectively P=0.10). Table 2. Univariate Model Multivariate Model OR(95% CI) P-value OR(95% CI) P-value Age (per 1-year increase) 0.92(0.88-0.95) &lt;0.001* 0.91(0.87-0.95) &lt;0.001* Disease duration (per 1-year increase) 0.97(0.97-1.02) 0.21 Concomitant MTX use (yes/no) 0.95(0.39-2.31) 0.91 Concomitant oral steroid use (yes/no) 1.84(0.76-4.42) 0.16 1.61(0.60-4.34) 0.349 Number of previous use of bDMARDs (per drug) 1.26(0.99-1.62) 0.05 1.39(1.05-1.84) 0.02* DAS-ESR at baseline (per 1 increase) 1.02(0.76-1.36) 0.92 LDA achievement at 1 year (yes/no) 0.56(0.76-1.49) 0.23 RF positive (yes/no) 0.91(0.32-2.56) 0.85 ACPA positive (yes/no) 0.76(0.27-2.18) 0.62 OR odds raio, 95% CI 95% confidence interval, MTX methotrexate, bDMARDs biologic disease-modifying antirheumatic drugs, ACPA anti-citrullinated protein antibodies, RF rheumatoid factor *P&lt;0.05 Conclusion: Our present study suggests that tofacitinib is effective in real-world settings even without concomitant MTX. Our results also suggest that for continuous use of tofacitinib without lack of efficacy, use tofacitinib earlier during switching strategy for RA patients who have failed to be treated with bDMARDs is better. Disclosure of Interests: None declared