Effect of dose adjustments on the efficacy and safety of tofacitinib in patients with rheumatoid arthritis: a post hoc analysis of an open-label, long-term extension study (ORAL Sequel)

INTRODUCTION/OBJECTIVES: We assess the impact of switching versus staying on the same tofacitinib dose on efficacy and safety in patients with rheumatoid arthritis (RA). METHODS: ORAL Sequel was an open-label, long-term extension study of patients with RA receiving tofacitinib 5 or 10 mg BID for up to 9.5 years. Tofacitinib doses could be switched during the study at investigator discretion. In this post hoc analysis, data from ORAL Sequel were stratified into four groups: 5 → 10 mg BID (Dose-up); 5 mg BID (Stay-on 5); 10 → 5 mg BID (Dose-down); and 10 mg BID (Stay-on 10). Efficacy assessments over 12 months included: change from baseline in 4-component Disease Activity Score in 28 joints, erythrocyte sedimentation rate (DAS28), and DAS28 minimum clinically important difference, remission, and low disease activity (LDA) rates. Safety was assessed for the study duration. RESULTS: Generally, DAS28 improvements and minimum clinically important difference rates were significantly greater (p < 0.05) in Dose-up versus Stay-on 5 up to month 12. DAS28 remission rates were significantly greater in Dose-up versus Stay-on 5 at month 12. Change from baseline in DAS28 was similar in Dose-down and Stay-on 10. No significant differences in DAS28 LDA rates were observed between groups. Safety data were similar overall across the four groups. CONCLUSION: In patients with RA receiving open-label tofacitinib, this analysis found that some benefited from increasing dose from 5 to 10 mg BID and did not find that reducing dose from 10 to 5 mg BID affected efficacy or that dose switching in either direction affected safety. STUDY REGISTRATION: ClinicalTrials.gov number NCT00413699. Registered December 20, 2006. https://clinicaltrials.gov/ct2/show/NCT00413699 SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10067-021-05908-z.