{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T09:46:14Z","timestamp":1779356774954,"version":"3.51.4"},"reference-count":68,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Therapeutic Advances in Musculoskeletal"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>To review treatment effectiveness and adverse events of calcineurin inhibitors (CNIs) such as cyclosporin A (CsA) and tacrolimus in patients with systemic sclerosis (SSc).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>A systematic literature search was performed on PubMed and Web of Science using the predefined keywords \u2018systemic sclerosis\u2019, scleroderma, cyclosporin*, and tacrolimus. Articles were eligible for inclusion, if SSc patients had been treated with CNIs and data on treatment effects were available.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>This systematic literature review identified 37 papers (19 case reports, 15 case series, 2 controlled studies, and 1 retrospective study) including 134 SSc patients treated with CNIs. In 34 of 37 papers, CsA was used. An improvement of skin fibrosis was observed in 77 of 96 (80.2%) patients using a wide variety of outcome measures and dose regimes. Both controlled studies showed significant improvements, one using a historical control group and one using a no-treatment control group. Improvement in pulmonary function tests (PFTs) occurred in 67.9% (19\/28) of the patients who had reduced PFTs at baseline. In 58 (43.3%) cases, adverse renal events were reported, of which 7 (5.2%) were severe such as scleroderma renal crisis (SRC), CsA-associated nephropathy, or death by renal insufficiency. Adverse events led to dose reduction, treatment interruption, or withdrawal in 39 of 134 (29.1%).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>In this systematic literature review, signals for potential effectiveness of CsA for skin and pulmonary fibrosis were found, but the evidence level of the identified studies was too low to allow robust conclusions. Randomized controlled double-blind trials are needed to conclude on the effectiveness of CNIs in SSc. Renal toxicity of CNIs was confirmed in this review and needs to be considered in the design of such studies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/1759720x221092374","type":"journal-article","created":{"date-parts":[[2022,5,19]],"date-time":"2022-05-19T08:53:13Z","timestamp":1652950393000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":8,"title":["Calcineurin inhibitors in systemic sclerosis \u2013 a systematic literature review"],"prefix":"10.1177","volume":"14","author":[{"given":"Nina N.","family":"Hofmann","sequence":"first","affiliation":[{"name":"Department of Rheumatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert A.","family":"Amb\u00fchl","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8114-8239","authenticated-orcid":false,"given":"Suzana","family":"Jordan","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oliver","family":"Distler","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, University Hospital Zurich, University of Zurich, Schmelzbergstr. 24, Zurich 8091, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2022,5,19]]},"reference":[{"key":"bibr1-1759720X221092374","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)30933-9"},{"key":"bibr2-1759720X221092374","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2008.106302"},{"key":"bibr3-1759720X221092374","doi-asserted-by":"publisher","DOI":"10.1007\/s00108-009-2405-z"},{"key":"bibr4-1759720X221092374","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-204424"},{"key":"bibr5-1759720X221092374","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200011)43:11<2445::AID-ANR11>3.0.CO;2-Q"},{"key":"bibr6-1759720X221092374","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200112)44:12<2828::AID-ART470>3.0.CO;2-U"},{"key":"bibr7-1759720X221092374","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2006.062901"},{"key":"bibr8-1759720X221092374","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2017-211448"},{"key":"bibr9-1759720X221092374","doi-asserted-by":"publisher","DOI":"10.1097\/00005792-198311000-00001"},{"key":"bibr10-1759720X221092374","doi-asserted-by":"publisher","DOI":"10.1007\/s12016-009-8191-5"},{"key":"bibr11-1759720X221092374","doi-asserted-by":"publisher","DOI":"10.1016\/S0889-857X(03)00016-4"},{"key":"bibr12-1759720X221092374","first-page":"156","volume":"32","author":"Nihtyanova SI","year":"2014","journal-title":"Clin Exp Rheumatol"},{"key":"bibr13-1759720X221092374","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2016-209909"},{"key":"bibr14-1759720X221092374","doi-asserted-by":"publisher","DOI":"10.1016\/S2665-9913(19)30144-4"},{"key":"bibr15-1759720X221092374","doi-asserted-by":"publisher","DOI":"10.1007\/s00108-019-00699-7"},{"key":"bibr16-1759720X221092374","doi-asserted-by":"publisher","DOI":"10.2147\/ITT.S82037"},{"key":"bibr17-1759720X221092374","doi-asserted-by":"publisher","DOI":"10.1136\/rmdopen-2017-000533"},{"key":"bibr18-1759720X221092374","unstructured":"Kurz A. 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