Clinical efficacy of tofacitinib in active ankylosing spondylitis and dynamic changes in gut microbiota: an exploratory descriptive four-case series with 16S rRNA sequencing analysis

Objective: To describe short-term clinical outcomes and safety of tofacitinib in four patients with active ankylosing spondylitis (AS) using real-world data, and to explore dynamic changes in gut microbiota before and after treatment. Methods: Four patients with active AS received oral tofacitinib 5 mg twice daily for 6 months. Disease activity [the bath ankylosing spondylitis disease activity index (BASDAI), the ankylosing spondylitis disease activity score calculated with C-reactive protein (ASDAS-CRP)], functional status [the bath ankylosing spondylitis functional index (BASFI)], back pain visual analog scale (VAS), inflammatory markers [CRP, erythrocyte sedimentation rate (ESR)], and adverse events were assessed at baseline and month 6. Paired stool samples were collected for 16S ribosomal ribonucleic acid (rRNA) sequencing to evaluate alpha/beta diversity and compositional changes. Results: After 6 months, all four patients showed marked improvement in disease activity and function: BASDAI decreased from 8.38 ± 0.52 to 2.60 ± 0.38; ASDAS-CRP from 3.85 ± 0.29 to 1.50 ± 0.26. CRP and ESR trended downward, and chest expansion increased. No serious adverse events were observed. Microbiota analysis revealed no consistent changes in alpha diversity or beta diversity clustering; however, individual-level shifts in genera such as Faecalibacterium, Alistipes, and Acidaminococcus were observed. Conclusion: In this exploratory descriptive case series, tofacitinib was associated with favorable short-term clinical outcomes in four patients with active AS. No serious adverse events were noted. Gut microbiota alterations were highly individualized and hypothesis-generating only. Larger controlled studies are warranted to explore potential gut-joint mechanisms.