Therapeutic potential of spironolactone in ankylosing spondylitis patients: Relation to disease activity and functional status

Abstract

Aim of the workSpironolactone with its anti-inflammatory and immunomodulatory properties due to inhibition of nuclear factor kappa B could have a therapeutic potential in ankylosing spondylitis (AS). The aim was to study the impact of spironolactone in active AS patients with an inadequate response to synthetic disease modifying antirheumatic drugs (sDMARDs). Patients and methodsSixty AS patients were randomized to receive 24 weeks of treatment with spironolactone (n = 30, 2 mg/kg/day) or placebo (n = 30) as an adjunct to existing stables DMARDs. Therapy results evaluated by assessment of inflammatory measures erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Bath AS disease activity index (BASDAI), AS disease activity score (ASDAS) and Bath AS functional index (BASFI), and proinflammatory cytokines (TNF-α,IL-6 and IL-1). Endothelial progenitor cells (EPCs), flow-mediated dilatation (FMD), oxidative measures (TBARS and serum nitrite) were assessed as surrogates for cardiovascular endpoints. ResultsAfter 24 weeks: inflammatory and disease activity measures ESR, CRP, ASDAS, BASDAI, and BASFI (All p < 0.001) were significantly reduced after treatment with spironolactone but did not show significant change in the placebo group (p > 0.05). Proinflammatory cytokines, TNF-α and IL-6, significantly reduced after treatment (both p < 0.001) in spironolactone arm. After 24 weeks treatment, surrogates of vascular function including EPCs, FMD and oxidative measures significantly improved in spironolactone treated patients. ConclusionSpironolactone in AS inhibits the proinflammatory cytokines and has antioxidative action, improves ESR and CRP with improvement in inflammatory disease activity. It reduces nitrite and improves EPC population with resultant improvement of endothelial dysfunction. Spironolactone has anti-inflammatory, immunomodulatory and vasculoprotective potential in AS.