Abstract
Objectives The objective was to evaluate the efficacy and safety of escalating tofacitinib from 10 mg to 15 mg daily in NSAID-refractory axial spondyloarthritis (ax-SpA) patients with inadequate 12-week response to 10 mg. Methods This was a pragmatic, open-label, single-arm, dose-escalation study (24 weeks). 101 patients were enrolled (ITT); 88 completed both week-12 and week-24 assessments (evaluable). All started tofacitinib 10 mg daily. At week 12, those achieving ASDAS-CRP (Ankylosing Spondylitis Disease Activity Score - C-reactive protein) major improvement (MI; Δ≥2.0) continued 10 mg; non-responders escalated to 15 mg. Outcomes included ASDAS-CRP (Clinically Important Improvement (CII)/MI/inactive disease), Assessment of SpondyloArthritis International Society criteria (ASAS 20/40), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Metrology Index (BASMI), Ankylosing Spondylitis Quality of Life (ASQoL), and 36-Item Short-Form Health Survey (SF-36); safety was monitored per Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Results Of the evaluable cohort (n=88), 57 (64.8%) achieved MI at week 12 and continued 10 mg; 31 (35.2%) escalated to 15 mg. By week 24, mean ASDAS-CRP improved from 4.4→1.7 (10 mg) and 4.0→2.2 (15 mg). In the escalation subgroup, ASDAS-CRP improved 3.0 ± 0.7→2.2 ± 0.7, BASDAI 3.9 ± 1.3→2.9 ± 1.2, and ASAS 20/40 responses rose to 93.5%/45.2%. Six patients discontinued due to AEs (5 transaminitis at ≤10 mg; 1 breast tumour). Rhinitis was more frequent with 15 mg (58.1% vs 31.6%). No TB, VTE, MACE, or deaths occurred. Conclusions In patients not meeting 12-week targets on 10 mg, escalation to 15 mg yielded additional clinically meaningful improvement with a safety profile generally comparable to 10 mg. Selective escalation may be a feasible treat-to-target strategy where alternatives are limited.