Background/Purpose: Aminaphtone (AMI) is a vasoactive drug licensed to treat microvascular disorders and able to increase peripheral blood perfusion and to reduce Raynaud’s phenomenon (RP) clinical symptoms (1,2). In vitro studies showed that AMI seems able to downregulate vasoconstrictor peptides, adhesion molecules and pro-inflammatory cytokine expression, including transforming growth factor beta (TGF-beta) (3,4).
The aim of the study was to test the effect of AMI treatment added to standard therapy on TGF-beta1 serum concentrations in systemic sclerosis (SSc) patients affected by active secondary RP.  

Methods: Twenty-six SSc patients according to the EULAR/ACR 2013 criteria (mean age 63±17 years; mean disease duration 11±5 years) were enrolled. Patients were on stable standard treatment since at least three months, before starting AMI 75 mg BID. All patients provided written informed consent to enter the study and for the management of the clinical data. Blood samples were collected at baseline (W0), after 3 (W3) and 12 weeks (W12), and were frozen (-80 °C) until assayed by ELISA (Ella automated immunoassay system) in triplicate to measure the endogenous level of the active form of TGF-beta1. Median values were reported as pg/ml, along with interquartile range (IQR). Laser speckle contrast analysis (LASCA) was also performed at W0, W3 and W12 to measure digital blood perfusion (2). Statistical analysis was carried out by non-parametric tests.  

Results: TGF-beta1 serum concentrations progressively decreased from W0 to W12 in AMI treated cohort of patients (median 7942 [IQR 13411], 7050 [7655], 5154 [3985] pg/ml, respectively at W0, W3 and W12. Freedman test, p=0.05). A strong statistically significant difference was observed comparing TGF-beta1 levels between W3 and W12 (Wilcoxon signed rank test, p=0.007). At all times, TGF-beta1 concentrations were found lower in SSc patients with better clinical response to AMI treatment, (increase of peripheral blood perfusion as assessed by LASCA) than in those with poorer clinical response, even if this difference was not statistically significant (median and [IQR] respectively at W0, W3 and W12 for better vs poorer responders: 6137 [14353] vs 10491 [29400], 5940 [13632] vs 10430 [25054], 4861 [7353] vs 5447 [3185] pg/ml). Results are limited by large biological variability of TGF-beta1 concentrations since evaluated in a small cohort of patients. No serious side effects due to AMI treatment were observed during the follow-up.  

Conclusion: In conclusion AMI treatment seems to contribute to reduce TGF-beta1 serum concentrations already at 12 weeks in SSc patients with active RP when added to the ongoing standard treatment. This observation is clinically stimulating, since TGF-beta is a profibrotic mediator involved in the pathophysiology of SSc. Present pilot evaluation is now followed by a larger/longer study including also control groups in order to correlate such effects with lung and skin clinical involvement.

References:  1. Gotelli E et al. Pharmaceuticals (Basel) 2023;16:569.  2. Ruaro B et al. Front Pharmacol 2019;10:293.  3. Salazar G et al. Eur J Pharmacol 2016;782:59–69.  4. Denton CP et al. Curr Opin Rheumatol 2001;13:505-11.

« Back to ACR Convergence 2024

ACR Meeting Abstracts - https://acrabstracts.org/abstract/effects-of-aminaphtone-on-tgf-beta1-serum-concentration-as-concomitant-treatment-to-standard-therapy-in-systemic-sclerosis-patients-a-pilot-study/