Background: Reactive arthritis (ReA) is an immune-mediated subtype of spondyloarthritis typically triggered by genitourinary or gastrointestinal infections. Current treatment strategies primarily rely on non-steroidal anti-inflammatory drugs (NSAIDs) and conventional synthetic DMARDs (csDMARDs), while biologic therapies are reserved for refractory cases. Despite advances in inflammatory arthritis, limited progress has been made in evaluating novel targeted or immunomodulatory agents for ReA. Iguratimod, an oral immunomodulatory drug approved for rheumatoid arthritis in several Asian countries, exhibits anti-inflammatory and cytokine-suppressive properties; however, clinical evidence supporting its use in ReA remains scarce.

Objectives: To evaluate the clinical efficacy and cytokine-modulating effects of Iguratimod in patients with Reactive Arthritis compared with csDMARD monotherapy and biologic therapy.

Methods: This 26-week prospective, open-label comparative cohort study included 60 adult patients aged 18–55 years with active Reactive Arthritis diagnosed according to Assessment of SpondyloArthritis International Society (ASAS) criteria following documented genitourinary or gastrointestinal infection. Active disease was defined as BASDAI ≥4 and/or ASDAS-CRP ≥2.1 despite prior NSAID therapy. Patients were consecutively enrolled and allocated into three treatment groups (n=20 each): Iguratimod 25 mg/day combined with sulfasalazine 2.0 g/day, adalimumab 40 mg administered subcutaneously every other week, or sulfasalazine 2.0 g/day monotherapy. Stable background NSAIDs were permitted, while systemic glucocorticoids exceeding 10 mg/day prednisone equivalent and other DMARDs were not allowed. Clinical outcomes including BASDAI, ASDAS-CRP, HAQ, and RAPID3 were assessed at baseline, week 13, and week 26. Laboratory evaluation comprised CRP and ESR, and serum levels of IL-17A and TNF-α were quantified by enzyme-linked immunosorbent assay. Safety and tolerability were monitored through clinical assessment and routine laboratory testing, including liver function parameters, at each visit. Statistical analyses involved within- and between-group comparisons over time, with results expressed as mean ± SD or percentage change and statistical significance defined as p < 0.05.

Results: At week 26, adalimumab achieved the highest clinical remission rate (63%), accompanied by pronounced reductions in inflammatory activity, including CRP (−18.2 mg/L), IL-17A (−41%), and TNF-α (−47%; p <0.01). Treatment with Iguratimod resulted in significantly greater improvements compared with sulfasalazine monotherapy, with a larger reduction in BASDAI scores (−3.4 ± 0.8 vs −1.7 ± 0.6, p <0.01) and ASDAS-CRP (−1.6 ± 0.4 vs −0.8 ± 0.3, p <0.05). Iguratimod was also associated with meaningful decreases in CRP (−12.6 mg/L), IL-17A (−28%), and TNF-α (−35%; p <0.05). Functional improvement was observed in 58% of patients receiving Iguratimod compared with 31% in the sulfasalazine group. Iguratimod was generally well tolerated; transient elevations in liver enzymes were the most frequently observed adverse events, without treatment discontinuation.

Conclusions: Iguratimod demonstrates clinically relevant anti-inflammatory and cytokine-modulating effects in patients with Reactive Arthritis, providing superior outcomes compared with csDMARD monotherapy and approaching the efficacy of biologic therapy. These findings suggest that Iguratimod may represent a promising emerging therapeutic option for ReA, particularly in settings where biologic access is limited, and support further evaluation in larger randomized controlled trials.

REFERENCES: NIL.

Acknowledgments: NIL.

Disclosure of Interests: None declared.