Therapeutic Outcomes of Tofacitinib with Dose Escalation Strategies in Patients with NSAID-Refractory Axial Spondyloarthritis

Tofacitinib in NSAID-Refractory Axial SpA

Abstract

Background: Axial spondyloarthritis (axSpA) is often resistant to first-line non-steroidal anti-inflammatory drugs (NSAIDs), necessitating the use of advanced therapies. Janus kinase (JAK) inhibitors have become highly effective oral alternatives to biological agents. In resource-limited settings like Bangladesh, the availability of lower-cost tofacitinib provides a crucial therapeutic option, reducing financial and accessibility barriers associated with biologics. Effective patient management in these contexts requires tailored dosing strategies to carefully balance efficacy, safety, and affordability.

Objective: To assess the therapeutic efficacy and safety of tofacitinib in patients with NSAID-refractory axSpA, with a particular focus on the outcomes of a dose-escalation strategy for patients showing an inadequate response to standard dosing.

Methods: This prospective clinical trial (NCT03738956) enrolled 52 patients with NSAID-refractory axSpA. All participants initially received tofacitinib 5 mg twice daily (Phase A, months 0–3). At the end of month 3, treatment response was evaluated: patients achieving a clinically important improvement in ASDAS-CRP (“ASDAS-CRP e” 1.1) were maintained on 5 mg twice daily for the remainder of the study (Phase B, months 3–6). For those who failed to achieve this threshold, the tofacitinib dose was escalated to 10 mg twice daily. The primary efficacy endpoint was the ASAS20 response rate. Secondary assessments, conducted at baseline, 1, 3, and 6 months, included ASAS40/70, BASDAI, BASFI, ASDAS, MASES, CRP, ESR, spinal pain, and fatigue. Adverse events (AEs) and serious adverse events (SAEs) were actively monitored. Statistical significance was determined using two-sided tests, with p < 0.05 considered significant.

Results: In this study, 52 patients (mean age 32.9 years, 78.8% male) were included. Tofacitinib demonstrated rapid and sustained efficacy; by month 3, overall ASAS20, ASAS40, and ASAS70 response rates were 73.1%, 65.4%, and 30.8%, respectively. Patients maintained on 5 mg twice daily (n=42) showed continued significant improvement at month 6 (ASAS20: 95.2%; ASAS40: 88.1%; ASAS70: 50.0%; all p<0.05). Ten patients (19.2%) with inadequate response at month 3 underwent dose escalation to 10 mg twice daily, achieving modest subsequent improvements by month 6 (ASAS20: 30%; ASAS40: 30%; ASAS70: 20%). All composite disease measures (including BASDAI, BASFI, and ASDAS-CRP) improved significantly from baseline (p<0.05). Adverse events occurred in 63.5% of patients, with serious adverse events, including herpes zoster and tuberculosis, reported in 13.5%.

Conclusions: Standard dosing of tofacitinib showed rapid response, high efficacy, and sustained disease control in NSAID-refractory axial spondyloarthritis. Those with a poor response to the standard dose may benefit from dose escalation, but caution is required as serious adverse events are relatively common. Clinicians should prioritise vigilant safety monitoring and carefully weigh the risks and benefits before increasing the dose in non-responders.

Bangladesh Medical Res Counc Bull 2026;52(1): 4-12