Long-term clinical stabilization of scleroderma patients treated with a chronic and intensive IV iloprost regimen
Rheumatol Int
Long?term clinical stabilization of scleroderma patients treated with a chronic and intensive IV iloprost regimen
Rosario Foti 0 1 3 4
Elisa Visalli 0 1 3 4
Giorgio Amato 0 1 3 4
Alessia Benenati 0 1 3 4
Giovanni Converso 0 1 3 4
Alberto Farina 0 1 3 4
Salvatore Bellofiore 0 1 3 4
Massimiliano Mul? 0 1 3 4
Marcella Di Gangi 0 1 3 4
0 Division of Cardiology, A.O.U. Policlinico Vittorio Emanuele , Catania , Italy
1 Rheumatology Unit, A.O.U. Policlinico Vittorio Emanuele , Catania , Italy
2 Rosario Foti
3 Division of General Thoracic Surgery, A.O.U. Policlinico Vittorio Emanuele , Catania , Italy
4 Medical Affairs Department, Italfarmaco S.p.A. , Milan , Italy
Intravenous iloprost is a first-line option for the treatment of scleroderma-related digital vasculopathy, and some studies have suggested its favourable role on disease progression. The aim of our study is to evaluate the disease progression, specifically in terms of cardiopulmonary function, in a group of consecutive patients chronically treated with intravenous iloprost. Our retrospective study enrolled 68 scleroderma patients (68 F, 54.4 ? 12.3 years) treated with iloprost for 7.1 ? 2.9 years, with a schedule of 5-6 consecutive daily infusions per month (6 h/day, 0.5-2.0 ng/ kg/min). In all patients, modified Rodnan skin score (4.7 ? 5.3 vs. 3.7 ? 5.3, p < 0.0001), systolic pulmonary arterial pressure (sPAP) (30.9 ? 6.4 vs. 24.0 ? 3.2 mmHg, p < 0.0001), tricuspid annular plane systolic excursion (22.1 ? 2.4 vs. 23.8 ? 3.5 mm, p = 0.0001), pro-brain natriuretic peptide (97.2 ? 69.3 vs. 65.8 ? 31.7 pg/ml, p = 0.0005) showed statistically significant improvement from baseline. In the subgroup of patients with baseline sPAP ?36 mmHg (n = 17), a significant sPAP reduction was observed (from 39.5 ? 3.8 to 25.1 ? 4.5 mmHg, p < 0.0001) after 7.6 ? 2.5 years of follow-up. The number of patients with digital ulcers (DUs) at follow-up was reduced from baseline (42.6 vs. 11.8%, p < 0.001), and none of the free-DU patients at baseline presented DUs at follow-up. An intensive and chronic regimen of IV iloprost administration seems to stabilize and potentially improve the long-term development of disease in SSc patients, as suggested by stabilization or significant improvement of cardiopulmonary parameters and vasculopathy.
Raynaud's phenomenon; Scleroderma; Iloprost; Systolic pulmonary arterial pressure; Digital ulcers
Introduction
Scleroderma (systemic sclerosis or SSc) is a severe, chronic
disease characterized by small vessel vasculopathy,
autoantibodies production, and fibroblast dysfunction leading to
an excessive deposition of collagen in the skin and internal
organs [
1, 2
].
Severe Raynaud?s phenomenon (RP) is the early onset
symptom in most SSc patients and may precede other
clinical manifestations of the disease by many years [
3
].
The clinical course of the disease often involves the
cardiovascular and respiratory systems, which can be severely
damaged by SSc. The heart can be directly or indirectly
involved, with myocardial damage, or with the involvement
of other organs, especially kidneys and lungs, respectively
[
4
]. For the respiratory system, SSc can affect lung
parenchyma and pulmonary blood vessels, leading to
interstitial lung disease (ILD), which may progress to pulmonary
arterial hypertension (PAH). The presence of a
cardio-pulmonary involvement generally leads to a poor prognosis
for the patient [
2
]. Patients with significant internal organ
involvement remain often asymptomatic until the late
stages of systemic sclerosis; therefore, routine monitoring
for the underlying disease and an intensive medical
treatment are essential after the first diagnosis. Despite recent
advances in the disease management, systemic sclerosis
remains a treatable but not curable disease [
2
].
In the present paper, we report our experience with
intravenous iloprost, a stable prostacyclin analogue
indicated for the treatment of secondary RP, which may have a
favourable effect on the disease progression. Iloprost shows
vasodilating, anti-platelet, cytoprotective, and
immunomodulating properties, with a long-lasting beneficial effect
on the microcirculation [
5
]. The European League Against
Rheumatism (EULAR) guidelines recommend iloprost
as a first-line drug for the treatment of SSc-related digital
vasculopathy in order to reduce the frequency and severity
of SSc-RP attacks and to heal active digital ulcers (DUs)
in patients with SSc, representing the gold standard in the
treatment of active ulcers [
6
]. Moreover, recent studies
have described a favourable disease course in SSc patients
regularly treated with iloprost, with a low occurrence of the
most severe vascular complications such as PAH, renal
crisis, and digital necrosis [
7?12
].
The aim of the present study is to evaluate the disease
progression, specifically in terms of cardiopulmonary
function, in a group of consecutive SSc patients treated with
iloprost, at t (...truncated)