{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T02:36:34Z","timestamp":1777689394205,"version":"3.51.4"},"reference-count":41,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T00:00:00Z","timestamp":1734912000000},"content-version":"vor","delay-in-days":357,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["International Journal of Rheumatology"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Systemic sclerosis\u2010associated Raynaud phenomenon (SSc\u2010RP) confers poor outcomes, including ulceration, gangrene, autoamputation, and hand disability. Prostaglandin analogues (PG) are a group of prostacyclin\u2010derived drugs with properties that may address underlying complex mechanisms of SSc\u2010RP. This systematic review and meta\u2010analysis evaluated the efficacy and tolerability of PGs in SSc\u2010RP.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> We systematically reviewed randomized control trials (RCTs) evaluating PG use in SSc\u2010RP. 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\u2010reported outcome measure (PROM\u2010VAS), and tolerability.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Eleven RCTs were included, reporting a total of <jats:italic>n<\/jats:italic> = 1081 individuals with SSc. PG confers a beneficial effect on RP severity in the short\u2010term, weighted Mean difference (WMD) \u22120.63 (95% CI \u22120.99, \u22120.27, <jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup> 0%), with no difference in tolerability compared to placebo OR 1.88 (95% CI 1.00, 3.55, <jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup> = 1<jats:italic>%<\/jats:italic>). PG has nonsignificant trends towards improvement in RP frequency WMD of \u22120.32 (95% CI \u22120.76, 0.13, <jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup> = 0<jats:italic>%<\/jats:italic>), RP duration WMD \u22124.78 (95% CI \u221214.69, 5.14, <jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup> = 1<jats:italic>%<\/jats:italic>), PROM\u2010VAS WMD \u22124.81 (95% CI \u221211.31, 1.69, <jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup> = 67<jats:italic>%<\/jats:italic>), and new or recurrent digital ulcers OR 0.92 (95% CI 0.48, 1.76, <jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup> = 34<jats:italic>%<\/jats:italic>).<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> 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\u2010RP outcomes.<\/jats:p>","DOI":"10.1155\/ijr\/1682081","type":"journal-article","created":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T12:05:22Z","timestamp":1734955522000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Efficacy and Tolerability of Prostaglandin Analogues in Treating Systemic Sclerosis\u2010Associated Raynaud Phenomenon: A Systematic Review and Meta\u2010Analysis"],"prefix":"10.1155","volume":"2024","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0833-9274","authenticated-orcid":false,"given":"Hana","family":"Alahmari","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hila","family":"Jazayeri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0591-2976","authenticated-orcid":false,"given":"Sindhu R.","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,12,23]]},"reference":[{"key":"e_1_2_11_1_2","first-page":"198","article-title":"Systemic sclerosis: an update","volume":"66","author":"Varga J.","year":"2008","journal-title":"Bulletin of the NYU Hospital for Joint Diseases"},{"key":"e_1_2_11_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2023.109267"},{"key":"e_1_2_11_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keab190"},{"key":"e_1_2_11_4_2","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2011-200742"},{"key":"e_1_2_11_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-020-0386-4"},{"key":"e_1_2_11_6_2","first-page":"1573","article-title":"Criteria for the classification of early systemic sclerosis","volume":"28","author":"LeRoy E. C.","year":"2001","journal-title":"Journal of Rheumatology"},{"key":"e_1_2_11_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kez558"},{"key":"e_1_2_11_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mvr.2014.05.007"},{"key":"e_1_2_11_9_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2010.135772"},{"key":"e_1_2_11_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2012.96"},{"key":"e_1_2_11_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/bf00614197"},{"key":"e_1_2_11_12_2","doi-asserted-by":"publisher","DOI":"10.1177\/153857449502900105"},{"key":"e_1_2_11_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780380206"},{"key":"e_1_2_11_14_2","first-page":"722","article-title":"Disease-modifying effects of long-term cyclic iloprost therapy in systemic sclerosis. A retrospective analysis and comparison with a control group","volume":"25","author":"Airo P.","year":"2007","journal-title":"Clinical and Experimental Rheumatology"},{"key":"e_1_2_11_15_2","first-page":"786","article-title":"Treatment of Raynaud\u2032s phenomenon with intravenous prostaglandin E1alpha-cyclodextrin improves endothelial cell injury in systemic sclerosis","volume":"28","author":"Gardinali M.","year":"2001","journal-title":"The Journal of Rheumatology"},{"key":"e_1_2_11_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/37.6.703"},{"key":"e_1_2_11_17_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.50.6.359"},{"key":"e_1_2_11_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.Cd000953"},{"key":"e_1_2_11_19_2","doi-asserted-by":"publisher","DOI":"10.5867\/medwave.2015.02.6082"},{"key":"e_1_2_11_20_2","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-204424"},{"key":"e_1_2_11_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.22965"},{"key":"e_1_2_11_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.20676"},{"key":"e_1_2_11_23_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2010.130658"},{"key":"e_1_2_11_24_2","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2014-207001"},{"key":"e_1_2_11_25_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.l4898"},{"key":"e_1_2_11_26_2","volume-title":"Review Manager (RevMan) 5.3","author":"Cochrane T.","year":"2008"},{"key":"e_1_2_11_27_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.327.7414.557"},{"key":"e_1_2_11_28_2","unstructured":"HBJS. GuyattG. Bro\u017cekJ. GuyattG. andOxmanA. GRADE Handbook for Grading Quality of Evidence and Strength of Recommendations. using the GRADE approach Updated October 2013. The GRADE Working Group.https:\/\/gradepro.org\/handbook."},{"key":"e_1_2_11_29_2","doi-asserted-by":"publisher","DOI":"10.5301\/jsrd.5000232"},{"key":"e_1_2_11_30_2","first-page":"2173","article-title":"Preventive effect of an oral prostacyclin analog, beraprost sodium, on digital necrosis in systemic sclerosis. French Microcirculation Society Multicenter Group for the study of vascular acrosyndromes","volume":"26","author":"Vayssairat M.","year":"1999","journal-title":"The Journal of Rheumatology"},{"key":"e_1_2_11_31_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.40242"},{"key":"e_1_2_11_32_2","first-page":"503","article-title":"Effects of long-term cyclic iloprost therapy in systemic sclerosis with Raynaud\u2032s phenomenon. A randomized, controlled study","volume":"19","author":"Scorza R.","year":"2001","journal-title":"Clinical and Experimental Rheumatology"},{"key":"e_1_2_11_33_2","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(199804)41:4<670::AID-ART14>3.0.CO;2-I"},{"key":"e_1_2_11_34_2","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/37.9.952"},{"key":"e_1_2_11_35_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.54.3.197"},{"key":"e_1_2_11_36_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-120-3-199402010-00004"},{"key":"e_1_2_11_37_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.298.6673.561"},{"key":"e_1_2_11_38_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.44.11.754"},{"key":"e_1_2_11_39_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.40.4.350"},{"key":"e_1_2_11_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2665-9913(19)30079-7"},{"key":"e_1_2_11_41_2","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics11060981"}],"container-title":["International Journal of Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/ijr\/1682081","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T12:05:26Z","timestamp":1734955526000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1155\/ijr\/1682081"}},"subtitle":[],"editor":[{"given":"Rishi","family":"Pal","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2024,1]]},"references-count":41,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,1]]}},"alternative-id":["10.1155\/ijr\/1682081"],"URL":"https:\/\/doi.org\/10.1155\/ijr\/1682081","archive":["Portico"],"relation":{},"ISSN":["1687-9260","1687-9279"],"issn-type":[{"value":"1687-9260","type":"print"},{"value":"1687-9279","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1]]},"assertion":[{"value":"2024-02-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"1682081"}}