# Efficacy of Tofacitinib in Refractory Axial Spondylarthritis: A Dose-Escalation Study

## TL;DR

This study found that increasing the dose of tofacitinib from 10 mg to 15 mg improved outcomes in patients with axial spondyloarthritis who did not respond well to the lower dose.

## Contribution

The study introduces a dose-escalation strategy for tofacitinib in NSAID-refractory axial spondyloarthritis patients.

## Key findings

- Escalation to 15 mg tofacitinib improved ASDAS-CRP scores and other disease activity measures.
- Safety profile of 15 mg was comparable to 10 mg, with no major adverse events like TB or VTE.
- 35.2% of patients escalated to 15 mg achieved significant improvements in disease activity and function.

## 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.