The Efficacy and Tolerability of Prostaglandin Analogues in Treating Systemic Sclerosis-Associated Raynaud Phenomenon: A Systematic Review and Meta-Analysis

Background: Systemic sclerosis-associated Raynaud phenomenon (SSc-RP) confers poor outcomes, including ulceration, gangrene, autoamputation, and hand disability. Prostaglandin analogues (PG) are a group of prostacyclin-derived drugs with properties that may address underlying complex mechanisms of SSc-RP. This systematic review and meta-analysis evaluated the efficacy and tolerability of PGs in SSc-RP. Methods: We systematically reviewed randomized control trials (RCTs) evaluating PG use in SSc-RP. The primary outcome was the severity of RP attacks. The secondary outcomes were the frequency and duration of RP attacks, healing of digital ulcers, development of new digital ulcers, change of capillary blood flow, patient health-reported outcome measure (PROM-VAS), and tolerability. Results: Eleven RCTs were included, reporting a total of n = 1081 individuals with SSc. PG confers a beneficial effect on RP severity in the short-term, weighted Mean difference (WMD) -0.63 (95% CI -0.99, -0.27, I ² 0%), with no difference in tolerability compared to placebo OR 1.88 (95% CI 1.00, 3.55, I ² = 1%). PG has nonsignificant trends towards improvement in RP frequency WMD of -0.32 (95% CI -0.76, 0.13, I ² = 0%), RP duration WMD -4.78 (95% CI -14.69, 5.14, I ² = 1%), PROM-VAS WMD -4.81 (95% CI -11.31, 1.69, I ² = 67%), and new or recurrent digital ulcers OR 0.92 (95% CI 0.48, 1.76, I ² = 34%). Conclusion: PGs are beneficial in the short term to reduce the RP severity and are tolerable. Larger, adequately powered trials are needed for higher certainty evidence across SSc-RP outcomes.