Long-term cyclic intravenous iloprost in systemic sclerosis: clinical experience from a single center

Abstract

The aim of the present study was to retrospectively evaluate response to therapy in 73 patients affected by systemic sclerosis (SSc) who underwent long-term cyclic treatment with intravenous iloprost for peripheral vascular involvement (average duration of treatment 54.12±41.04 months). Seventy-three SSc patients were enrolled. Data were collected by reviewing clinical records and by phone or direct interview. Patients underwent a thorough physical examination at the end of follow up. The incidence of severe vascular manifestations was also assessed. Statistical analysis was performed by Wilcoxon's signed rank test and descriptive statistics using Statview software. In this study cohort, 55 of 73 (75.2%) patients had a history of ischemic digital ulcers (DUs); 28 patients (38.4%) had active DUs at the beginning of treatment. Skin ulcers healed completely in 25 of 28 patients (89.3%) at the end of the first treatment. However, 40 of 55 patients (72.6%) relapsed after an average of 24 months. There was a significant correlation between relapse rate and/or number of ulcers and clinical factors (diffuse subset, changes in results of Allen's test, NT-pro BNP levels). The annual incidence of pulmonary arterial hypertension (PAH) was 2.34 (95%CI: 0.94-4.83) per 100 person years, the rate of gangrene was 2.7%, and no cases of scleroderma renal crisis were recorded. The incidence of PAH and of digital gangrene was higher than that observed in unselected SSc case series. These data suggest that our patients treated with iloprost have a higher vascular involvement than large case series of unselected SSc patients. A number of clinical factors are correlated to the severity of vascular involvement and could have an impact on the response to therapy. The clinical significance of these findings requires clarification and further investigation is needed.

Treatment of digital ulcers in systemic sclerosis: recent developments and future perspectives

“…Most patients on monthly iloprost infusions experience complete clinical resolution in the first year of treatment with the 10-year survival rate reaching in one cohort 55.6% [ 13 ]. In the absence of tools such as capillaroscopy, which require a certain level of experience and are operator dependent, simple clinical tests such as Allen’s test that can be performed easily at bedside can be employed as predictors of patient outcome; DUs in patients with a negative Allen’s test show expedited healing times [ 14 ]. Clinical improvement and a switch to easier, more cost-efficient ways of administration such as an elastomeric pump seem to be the main reasons of drug discontinuation [ 13 ].…”

“…No severe side effects reported. Martins et al/2022 [ 13 ] Observational retrospective study dSSc:9, lSSc: 37 60 N/A 44 Monthly infusion at 0.5–1.5 ng/kg /min, infusion rate as tolerated starting at 4 mL/h and increased by increments of 4 up to 16 mL/h 86.4% of patients: DUs healing in the first 6 months Safety: generalised erythroderma in one patient, others with minor AEs, 5-year survival rate: 68.2% Casigliani et al/2012 [ 14 ] Observational retrospective study dSSc: 31, lSSc: 42 73 N/A 28 Monthly infusion at 0.5–1.5 ng/kg /min, infusion rate as tolerated Complete healing in 89.4% of the patients after the first treatment Jamart/2022 [ 16 ] Observational longitudinal retrospective study dSSc:10, lSSc: 31 41 D2 13 Iloprost Infusion > 5 days vs. < 5 days Median infusion rate of 1.7 ng/kg/min. Number of patients with complete DU healing at day 90 was significantly higher among patients who received > 5 days of iloprost: 51 vs. 37% ( p < 0.05).…”

Correlation between Microvascular Damage and Internal Organ Involvement in Scleroderma: Focus on Lung Damage and Endothelial Dysfunction

“…Interestingly, NVC is applicable to follow the effects of treatments used in SSc. However, there are currently only a few pilot studies (nonrandomized, nondouble-blind, and nonplacebo-controlled) on this topic [15,[61][62][63][64][65][66][67][68][69].…”

<p>Management of digital ulcers in systemic sclerosis</p>

“…23 Unfortunately, iloprost and other prostanoids have a short half-life and pharmacological effect, 24 and cyclical repetitions of therapy are needed. 25 On the basis of these results, European League Against Rheumatism (EULAR) guidelines state that iloprost IV (0.5-2 ng/kg/min 6-8 hours per day for 3-5 consecutive days) should be considered in the treatment of DUs in SSc patients (strength of recommendation: A). 26 Regarding dosage, there is evidence that low-dose (0.5 ng/kg/min) and high-dose (2 ng/kg/min) iloprost have substantially the same effectiveness in long-term treatment.…”

“…27 Multiple studies have shown that administration of a mean iloprost dose of 1 ng/kg/min results in well-tolerated therapy without losing clinical efficacy. 8,23,[25][26][27] As the results of the medical literature are not homogeneous, iloprost administration dose has to be tailored in accordance with the patient's individual tolerability.…”