Background/Purpose: Raynaud’s phenomenon (RP) is a pivotal manifestation of systemic sclerosis (SSc) which reflects an underlying vasculopathy. Endothelial activation with increased circulating levels of Endothelin-1 (ET1) are frequently observed in SSc patients due to a deranged vascular homeostasis. Aminaftone (AMNA) –a derivate of the 4-aminobenzoic acid- was found to be capable of reducing the production of ET-1 in endothelial cell cultures. The present work was conducted to assess the role of AMNA in the treatment of RP and vasculopathy secondary to SSc.

Methods: Single-centre, randomized, prospective, double-blinded comparison of AMNA vs placebo. Patients received either 75 mg AMNA 3 times per day for 12 weeks in wintertime, or matching doses of placebo. We compared the number and the severity of RP attacks at baseline and after 12 weeks; furthermore we investigated the effect of AMNA on serum concentrations of ET1.

Results:  Twenty-five patients were randomized to receive AMNA or placebo; 23 patients (12 AMNA; 11 placebo) did complete the study; no drug-related averse events were observed. The two distinct groups were statistically overlapping for baseline clinical and demographical characteristics. An encouraging and strong trend on the reduction of the number of RP attacks in the AMNA vs placebo group  was observed (median: – 67.9% [-40.7%, -83.3%] vs -44.2% [-15.5%,-54.3%]; p=0.06; Mann-Whitney test); no differences in RP severity scores or Rp duration scores were observed. ET-1 serological concentrations were markedly reduced in the treatment arm compared to the placebo arm (median [IQR]: -43.5% [-25.5%, -46.2%] vs 4.9% [-0.6%, 15.9%]; p=0.02; Mann-Whitney test).

Conclusion: Although the primary clinical endpoint was not met, most likely due to the low sample size, AMNA was found to have meaningful effects on ET-1 serum levels. In light of the results of a previous report showing the non-inferiority of AMNA compared to bosentan in the log-term control of peripheral SS-related vascular clinical manifestations, when bosentan was not indicated, we believe that further wider and more focused studies (e.g. on the prevention of DU) may be warranted to investigate the long-term effect of AMNA in SSc.

References

Parisi S, et al. Efficacy of Aminaftone in the Treatment of Raynaud’s Phenomenon in Patients with Systemic Sclerosis: a Preliminary Study. EULAR 2013, SAT0218 abstract.

Scorza R, et al. Aminaftone, a derivative of 4-aminobenzoic acid, downregulates endothelin-1 production in ECV304 Cells: an in vitro Study.Drugs R&D 2008;9(4):251-7.

---

« Back to 2013 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/effect-of-aminaftone-on-raynauds-phenomenon-secondary-to-systemic-sclerosis-a-double-blind-prospective-randomized-placebo-controlled-pilot-study/