Background/Purpose:

Synthetic disease-modifying antirheumatic drugs (DMARDs) though effective have limitations often requiring use of expensive parenteral biologic DMARDs in Rheumatoid Arthritis (RA). Hence there is a need for safe, efficacious economical therapies for management of disease and its co-morbidities. Anticytokine therapy with Biologic DMARDs is efficacious but has limitations. Given the TNF inhibiting potential of spironolactone (SPIR)^1-2, We therefore investigated the anti-inflammatory effects of SPIR in RA patients in a  randomized, placebo-controlled, open label study.

Methods:

We organized a 24-week study on 70 patients (36 in SPIR and 34 in placebo arm) with active RA. They were randomized to oral SPIR (2 mg/kg/day) or placebo for 24 weeks as an adjunct to existing stable DMARD regimen. Therapy results were evaluated by ESR, CRP, Disease Activity Score in 28 joints (DAS28), simple disease activity index (SDAI), ACR response criteria and pro-inflammatory cytokines (TNF-α, IL-6 and IL-1). Flow mediated dilatation (FMD) was assessed by AngioDefender^™ and carotid intima media thickness (CIMT) of brachial artery. Endothelial progenitor cells (EPCs) (CD34⁺/CD133⁺) were quantified by flow cytometry.  Quality of life was assessed using HAQ-DI. 

Results:  At 24 weeks; ESR, CRP, DAS-28 and SDAI significantly (p<0·05) improved in SPIR group compared with placebo (Table 1).  At 24 weeks, more patients in the 2 mg/kg/day SPIR group than in the placebo group had an ACR20 response 47.5% (n=16) versus 25% (n=8). ACR50 response rates were 23% (n=8) and 6.2 % (n=2), respectively, in the SPIR and placebo groups, and ACR70 rates were 11.7% (n=4) and 2.9% (n=1).  At 24weeks, TNF-α, IL-6 and IL-1 improved significantly in SPIR compared with placebo (Table 1). With SPIR treatment the mean value of the FMD improved from 6.5 to 8.9 (p<0·001) and with placebo from 7.56 to 7.7 (p=0·12).  SPIR significantly improved EPC population (p=0.008) compared with placebo (p=0.305) after treatment. After 24 weeks, CIMT was significantly improved in SPIR (p=0.03) compared with placebo (p=0.30) (Table 1). At 24 weeks, HAQ disability index score was significantly improved in SPIR compared to placebo group (table 1). Two patients in the SPIR and 1 patient experienced adverse events or discontinued treatment because of adverse events.

Conclusion: These results suggest that SPIR is a powerful anti-inflammatory agent that significantly reduces inflammatory biomarkers and disease severity and improves physical function in RA. It also improves endothelial dysfunction, EPC population and CIMT indicating its beneficial effects on the enhanced cardiovascular risk of RA. SPIR could therefore possibly be used as an adjunct therapy with DMARDs in patients with RA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/spironolactone-as-a-novel-dmard-in-rheumatoid-arthritis/