Switching from adalimumab to tofacitinib in the treatment of patients with rheumatoid arthritis

Abstract

Background: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). The aim of this study was to explore the safety and efficacy of open-label tofacitinib following blinded treatment with adalimumab or tofacitinib for moderate to severe RA.

Methods: Analyses included patients treated with adalimumab 40 mg once every 2 weeks or tofacitinib 10 mg twice daily (BID) with background methotrexate (MTX) in a 12-month randomized study (NCT00853385), who subsequently received tofacitinib 10 mg BID (with/without background MTX) in an open-label extension (NCT00413699). Patients with treatment-related serious adverse events (AEs) and serious or recurrent infections in the index study were excluded from the extension study. Exposure-adjusted incidence rates of safety-related events were assessed in 3-month and 12-month periods in the year before and in the year after switching. Efficacy was assessed 3 months before, at the time of, and 3 months after switching.

Results: There were 233 (107 adalimumab to tofacitinib 10 mg BID, 126 blinded to open-label tofacitinib 10 mg BID) patients included in these analyses. Patients in both treatment sequences had similar incidence rates (per 100 patient-years) of discontinuation due to AEs, serious AEs, and serious infections in the year before and in the year after switching. Incidence rates of AEs were increased in the first 3 months after switching compared with the last 3 months before switching in both treatment groups. Switching from either blinded adalimumab or tofacitinib to open-label tofacitinib resulted in numerically higher incidence of responders for signs and symptoms of disease and improved physical function.

Conclusions: Treatment can be directly switched from adalimumab to tofacitinib. A similar safety and efficacy profile was seen when patients received open-label tofacitinib after receiving either blinded adalimumab or tofacitinib.

Trial registration: ClinicalTrials.gov Identifiers: NCT00853385 , registered 27 February 2009; NCT00413699 , registered 18 December 2006.

Keywords: Adalimumab; Drug switching; Efficacy; Rheumatoid arthritis; Safety; Tofacitinib.

Figures

Fig. 1

American College of Rheumatology (ACR) response rates 3 months before switch, at switch, and 3 months after switch*. ADA adalimumab, BID twice daily. *Includes patients who completed treatment with ADA 40 mg Q2W or tofacitinib 10 mg BID in ORAL Standard (or discontinued treatment for reasons other than a tofacitinib-related serious AE) and then enrolled in ORAL Sequel and switched treatment with minimal washout (≤2 weeks after their last dose of study drug in ORAL Standard). ACR, American College of Rheumatology; ACR20/50/70, 20/50/70% reduction in the number of tender and swollen joints, as well as 20/50/70% improvement in ≥3 of the other five ACR components; ADA, adalimumab; BID, twice daily; Q2W, every 2 weeks

Fig. 2

Disease Activity Score for 28-joint counts based on the erythrocyte sedimentation rate (DAS28-4(ESR)) and changes from baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) 3 months before switch, at switch, and 3 months after switch*. ADA adalimumab, BID twice daily. *Includes patients who completed treatment with ADA 40 mg Q2W or tofacitinib 10 mg BID in ORAL Standard (or discontinued treatment for reasons other than a tofacitinib-related serious AE) and then enrolled in ORAL Sequel and switched treatment with minimal washout (≤2 weeks after their last dose of study drug in ORAL Standard). Lower scores indicate less disease activity (DAS28–4[ESR]) or lower disability (HAQ-DI). ADA, adalimumab; BID, twice daily; DAS28–4(ESR), Disease Activity Score for 28 joint counts based on the erythrocyte sedimentation rate; HAQ-DI, Health Assessment Questionnaire-Disability Index; Q2W, every 2 weeks; SE, standard error. (a) Changes from Baseline in Disease Activity Score for 28-joint counts based on Erythrocyte sedimentation rate (DAS28-4(ESR) 3 months before switch, at switch, and 3 months after switch.* (b) Changes from Baseline in the Health Assessment QUestionnaire-Disability Index (HAQ-DI) 3 months before switch, at switch, and 3 months after switch*