1518: Efficacy and Safety of Prostaglandins Analogues in Systemic Sclerosis-associated Raynaud’s Phenomenon. a Systematic Review and Meta-Analysis

Hana Alahmari¹, Hila Jazayeri² and Sindhu Johnson³, ¹Toronto Scleroderma Program, Mount Sinai Hospital, Toronto Western Hospital, Division of Rheumatology, Department of Medicine, University of Toronto, Toronto, ON, Canada, ²University of Toronto, Toronto, ON, Canada, ³Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, ON, Canada

Background/Purpose: Raynaud's phenomenon (RP) is a vasculopathic manifestation of Systemic Sclerosis (SSc) that can lead to digital ulceration, gangrene, autoamputation, and hand disability. Prostaglandin analogs are prostacyclin-derived medications with potent vasodilatory properties. We conducted a systematic review and meta-analysis evaluating the efficacy and tolerability of prostaglandin analogs in controlling RP among SSc patients.

Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) of adults with SSc-associated RP with or without digital ulcers. The exposure was any prostaglandin compared to placebo or active control. The primary outcome was the effect on RP frequency. Secondary outcomes included RP severity, duration of RP attacks, healing of digital ulcers, development of new digital ulcers, change of capillary blood flow, impact on the patient's health-reported outcome, and tolerability. The time points were divided into short-term-follow (< 16 weeks) and long-term follow-up (≥ 16 weeks). The statistical analysis used RevMan software. Data were reported as pooled weighted mean difference (WMD) or odds ratio (OR) with 95% confidence intervals (95%CI). The study was compliant with PRISMA-S 2020 guidelines.

Results: Our search yielded 11 RCTs, of which ten were parallel, and 1 was crossover design. The studies were published between 1981 and 2017 and included five PGs (iloprost n=6, PGE1 n=2, baroprost n=1, trepinostil n=1, and selexipag n=1), often against a placebo. Most of the studies were conducted during winter to eliminate seasonal variability as a confounder. We performed meta-analyses using -effects models. PG significantly reduced RP severity in the short-term WMD -0.63 (95%CI -0.99, -0.27)]. In addition, there were trends for PG to reduce the frequency of RP attacks WMD -0.32 (95%CI -0.76, 1.13), and duration of attacks WMD -4.78 (95%CI -14.69, 5.14) but were not statistically significant. Withdrawal from trials due to adverse events was considered an indirect measure of drug intolerability. PGs increase the odds of withdrawal by 88%, OR 1.88 [95% CI 1.00, 3.55]. The most common adverse effects were postural hypotension, flushing, and headache. The quality of evidence ranged from moderate to low.

Conclusion: PGs can be beneficial in the short term to reduce the severity of SSc-associated RP. Therefore, PG may be considered a therapeutic option in people with SSc-associated RP.


H. Alahmari: None; H. Jazayeri: None; S. Johnson: None.