Does Sulfasalazine Still Have Therapeutic Value in the Treatment of Axial Spondyloarthritis? A Real‐World Cohort Study From China

ABSTRACT Objective The efficacy of sulfasalazine (SSZ) in axial spondyloarthritis (ax‐SpA) patients meeting both 2009 ax‐SpA and 2011 peripheral SpA (p‐SpA) criteria is unclear. This study aimed to assess SSZ's clinical efficacy in pure ax‐SpA and overlapping ax‐SpA patients and to identify factors influencing peripheral symptom development. Methods SpA patients from 2016 to 2023 at the First Medical Center of People's Liberation Army General Hospital were categorized into pure ax‐SpA and ax‐SpA with peripheral features. They received nonsteroidal anti‐inflammatory drugs (NSAIDs) alone or with SSZ. The study evaluated SSZ's efficacy, peripheral symptom timing and prevalence, and factors affecting symptom onset using Cox regression. Results Of 670 SpA patients, 469 maintained pure axial involvement throughout follow‐up, while 201 developed peripheral symptoms during follow‐up. had pure ax‐SpA. The SSZ plus NSAIDs group demonstrated significantly lower Axial Spondyloarthritis Disease Activity Score than NSAIDs‐only in both pure axial (1.2 vs. 1.8; p = 0.015) and axial‐with‐peripheral subgroups (1.1 vs. 1.8; p = 0.011). New peripheral symptoms occurred in 33.2% of the NSAIDs group and 15.1% of the SSZ plus NSAIDs group. SSZ reduced the risk of peripheral symptom development (hazard ratio [HR] = 0.489, p = 0.0028). In the Cox proportional hazards model adjusted for age, sex, smoking status, body mass index, and Human Leukocyte Antigen B27 status, male gender (HR = 0.64, p = 0.020) and SSZ use (HR = 0.47, p = 0.004) emerged as protective factors, whereas smoking significantly increased risk (HR = 1.97, p < 0.001). Conclusions SSZ reduces disease activity, improves quality of life among ax‐SpA patients, reduces the incidence of peripheral symptoms, and delays their onset. About one‐third of ax‐SpA patients develop peripheral symptoms over time, which are associated with poorer functional status and quality of life. Smoking increases this risk, while male gender and SSZ use offer protection.