Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement

The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.


Aminaftone Enhances Iloprost Beneficial Effects in Patients with Systemic Sclerosis and Recurrent Ulcers

Scorza,  Raffaella, Caronni,  Monica, Santaniello,  Alessandro, Toussoun,  Karen, Beretta,  Lorenzo

Purpose:

Endothelin-1 (ET-1) and adhesion molecules overexpression plays a pivotal role in the pathogenesis of vascular remodelling that characterizes systemic sclerosis (SSc). Indirect observations indicate that ET-1 is relevant in the pathogenesis of digital ulcers (DU) in scleroderma subjects. Treatment of digital ulcers in SSc patients is challenging as in many patients they tend to be chronic and relapse and largely affect the quality of life, in spite of efficacious pharmacological treatment like prostanoids and the dual ET-1 receptor blocker. In this study we investigated whether aminaftone that downregulates in vitro ET-1 (1) production and ex vivo expression of endothelial adhesion molecules (2) should favour ulcers' healing in SSc patients with recurrent and/or refractory ulcers resistant to cyclic iloprost treatment.

Method:

Thirteen patients referring to our outpatient clinic (11 females and 2 males) with diagnosis of SSc according to ACR criteria where included in this study. Five patients had a diagnosis of dcSSc, 8 a diagnosis of lcSSc. Mean age ± s.d. was 54 ± 10 years (range 35–69); disease duration (mean ± s.d.) was 9 ± 5 years. All the patients had chronic and/or recurrent digital ulcers (number of active ulcers/patients 2,43 ± 1,02) in spite of the chronic treatment with cyclic iloprost (2ng/kg/min for 8 hrs every 4 weeks). Iloprost treatment duration (mean ± s.d.) was 6 ± 1 years (range 5–9). All the patients had careful information about aminaftone, its usual therapeutical use in capillary disorders and gave informed consent to the treatment with oral aminaftone (75 mg t.i.d.), in addition to cyclic iloprost treatment. The duration of the aminaftone treatment was 12 months. The effect of aminaftone in enhancing Iloprost effect was analyzed by Students' T-test for paired samples.

Results:

The addition of aminaftone to cyclic Iloprost treatment in patients with refractory/relapsing digital ulcers favoured the healing (number of ulcers pre- and post-treatment: 2,43 ± 1,02 Vs 1,29 ± 0,61, p<0.005).

Conclusion:

These results show that aminaftone is able to increase the beneficial effects of iloprost in the management of digital ulcers secondary to SSc, supposedly by its capability to reduce ET-1 production and adhesion molecule expression. Further randomized study are needed to confirm whether this cheap and well tolerated drug is effective in association with conventional therapy to favour the healing of digital ulcers.

1.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;9:251–7.

2.Scorza, R, et al. Effects of aminaftone 75 mg TID on soluble adhesion molecules: a 12-week, randomized, open-label pilot study in patients with systemic sclerosis. Clin Ther. 2008;30:924–9.

To cite this abstract, please use the following information:
Scorza, Raffaella, Caronni, Monica, Santaniello, Alessandro, Toussoun, Karen, Beretta, Lorenzo; Aminaftone Enhances Iloprost Beneficial Effects in Patients with Systemic Sclerosis and Recurrent Ulcers [abstract]. Arthritis Rheum 2009;60 Suppl 10 :1738
DOI: 10.1002/art.26812

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