Tofacitinib in early active axial spondyloarthritis: protocol of a randomized double-blind, placebo-controlled, multicenter phase IV study, FASTLANE

Background: Early treatment initiation is one of the strongest predictors of good treatment response in axial spondyloarthritis (axSpA). Recently, the Assessment in SpondyloArthritis International Society (ASAS) defined early axSpA as a diagnosis of axSpA with a duration of axial symptoms equal to or less than 2 years. Tofacitinib is a Janus kinase (JAK) inhibitor for the treatment of ankylosing spondylitis. Objectives: Compare the efficacy and safety of tofacitinib versus placebo (both on non-steroidal anti-inflammatory drug (NSAID) background) in patients with active early axSpA and inadequate response to at least one NSAID. Design: This is a phase IV, randomized, double-blind, placebo-controlled, multicenter clinical trial. Methods and analysis: The study will recruit 104 patients aged >= 18 and <= 45 years with active early axSpA (chronic back pain <= 2 years), inadequate response to at least one NSAID, and objective signs of active inflammation (on magnetic resonance imaging (MRI) of sacroiliac joints (SIJs) or elevated C-reactive protein). Patients will be randomized 1:1 to receive tofacitinib 5 mg twice daily or placebo, with background naproxen 500 mg twice daily for 16 weeks. Patients not meeting early treatment response criteria at week 4 will receive open-label tofacitinib until week 16. Primary and key secondary endpoints at week 16 will be the proportion of patients achieving disease remission (Axial Spondyloarthritis Disease Activity Score <1.3) and change from baseline in MRI SIJ Spondyloarthritis Research Consortium of Canada osteitis score, respectively. Safety will be monitored up to 4 weeks after the last study drug dose. Ethics: The study will be performed according to the ethical principles of the Declaration of Helsinki and will be approved by independent ethics committees of each center. Discussion: This is one of the first randomized clinical trials designed to evaluate the efficacy and safety of a JAK inhibitor in the recently ASAS-defined "early" axSpA population. Trial registration: ClinicalTrials.gov: NCT06112665; CTIS: 2023-505050-18-00. Discussion: This is one of the first randomized clinical trials designed to evaluate the efficacy and safety of a JAK inhibitor in the recently ASAS-defined "early" axSpA population. Trial registration: ClinicalTrials.gov: NCT06112665; CTIS: 2023-505050-18-00.