AB0546 IMMEDIATE TO INTERMEDIATE EFFICACY AND SAFETY OF PROSTAGLANDINS E1 (PGE1) INHIBITORS- ALPROSTADIL IN TREATMENT OF SYMPTOMATIC RAYNAUD’S IN SYSTEMIC SCLEROSIS; SINGLE TERTIARY RHEUMATOLOGY CENTRE EXPERIENCE FROM SRI LANKA
Authors: S. H. Atukorale, K. Thilakarathne, I. Piyadasa, R. Rathnayake, P. Suriyagoda, B. Mahesh
Journal: Annals of the Rheumatic Diseases (2020)

Background: Systemic sclerosis (SSc) is a multi-system connective tissue disease 1 . Raynaud phenomenon (RP) is a frequent (&gt;90%) manifestation in SSc 2 &amp; if untreated could lead to complications such as digital ulcers, gangrene and amputation. Calcium antagonists are considered as first-line therapy for symptomatic SSc-RP. In refractory cases phosphodiesterase type 5 (PDE-5) inhibitors- Sildenafil and PGI2 analogue- Iloprost are used. A meta-analysis of trials indicate that PDE-5 inhibitors reduce the frequency and severity of SSc-RP attacks. In addition a study done with PGE1 inhibitors- Alprostadil 60 micrograms infusion given for six consecutive days, had shown immediate efficacy in SSc- RP; as demonstrated by increased blood flow, digitally measured by telethermography. Furthermore there was a reduction of the number, frequency and severity of attacks 3 . Due to unavailability of Iloprost in Sri Lanka, based on the above evidence some rheumatology centres use Alprostadil 60 microgram infusion for 3 consecutive days in refractory symptomatic SSc-RP. Objectives: To assess immediate (Day 4) and intermediate (Day 42) efficacy of Alprostadil 60 microgram infusions given for 3 consecutive days in treating SSc-RP. Methods: An observational longitudinal study was conducted at the Rheumatology unit, Teaching Hospital Anuradhapura- Sri Lanka during 01.09.2019- 30.12.2019. Twelve diagnosed Systemic Sclerosis patients with symptomatic Raynaud’s (Raynaud’s score of &gt;5) despite receiving maximum tolerable doses of calcium antagonists consisted of the study sample. Pre and post (on day 4 and 42) treatment frequency of Raynaud’s attacks and Raynaud’s score was recorded using a pre-tested interviewer administered questionnaire. Statistical analysis was done using SPSS version 22 with Wilcoxon Signed Rank test at 5% significance level. Results: All recruits were females (n=12). Median (IQR) age of the study population and disease-duration were 45 (40 to 53.5) years and 6 (2.8 to 9.5) years respectively. Among participants, 58.3% and 25% had previous or current digital ulcers and gangrene respectively. Table 1. Pre and post treatment mean frequency of attacks and mean Raynaud’s score Pre treatment median (IQR) Post treatment Day 4 median (IQR) and significance of the difference between the pre-treatment values Post treatment Day 42 median (IQR) and significance of the difference between the pre-treatment values Mean frequency of Raynaud’s attacks/ past 24hrs 4.0 (2.3 to 5.0) 0.0 (0.0 to 1.0) P&lt;0.05* 2.0 (0.3 to 3.8) P&lt;0.05* Mean duration of attack/24hrs 21.3 (1.1 to 32.5) 0.5 (0.5 to 3.0) P&lt;0.05* 7.5 (3.0 to 25.0) P&gt;0.05 Mean Raynaud’s score 6.5 (5.0 to 8.8) 2.0 (0.3 to 2.8) P&lt;0.05* 3.0 (0.1 to 5.0) P&lt;0.05* *statistically significant Conclusion: Alprostadil 60 microgram infusions demonstrated a statistically significant immediate and intermediate efficacy in treating symptomatic SSc- RP with reduction of frequency of Raynaud’s attacks and Raynaud’s score at both. Only immediate efficacy was seen for mean duration of attacks. Based on these and the observed satisfactory safety level, we recommend the use of Alprostadil for symptomatic Raynaud’s in SSc-RP as an alternative to Iloprost. Further studies of larger samples are recommended. References: [1]Kowal-Bielecka O, Fransen J, Avouac J EUSTAR Coauthors, et al Update of EULAR recommendations for the treatment of systemic sclerosis. Annals of the Rheumatic Diseases 2017;76:1327-1339 [2]Carpentier P, Satger B, Poensin D, et al. Incidence and natural history of Raynaud phenomenon: a long-term follow-up (14years) of a random sample from the general population. J Vasc Surg 2006;44:1023–8 [3]Bartolone S, Trifiletti A, DeNuzzo G. Efficacy evaluation of prostaglandin E1 against placebo in patients with progressive systemic sclerosis and significant Raynaud’s phenomenon. Minerva Cardioangiol 1999; 47: 137–143 Disclosure of Interests: None declared