{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T22:58:04Z","timestamp":1781737084460,"version":"3.54.5"},"reference-count":17,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,4,15]],"date-time":"2021-04-15T00:00:00Z","timestamp":1618444800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,4,15]],"date-time":"2021-04-15T00:00:00Z","timestamp":1618444800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH\/NIAMS K23","award":["K23 AR071473"],"award-info":[{"award-number":["K23 AR071473"]}]},{"DOI":"10.13039\/100001845","name":"Scleroderma Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001845","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015629","name":"Jerome L Greene Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100015629","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Martha McCrory Professorship"},{"name":"chresanthe stauralaukis memorial discovery fund"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Gastroenterol"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Lower gastrointestinal (GI) tract involvement can affect up to 50% of systemic sclerosis (SSc) patients, and may result in malabsorption, pseudo-obstruction, hospitalization, and death. We report our experience with linaclotide, a selective agonist of guanylate cyclase C (GC-C), for SSc patients with refractory lower GI disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed an analysis of patients seen at the Johns Hopkins Scleroderma Center and identified patients prescribed linaclotide for refractory lower GI manifestations. Patients had clinical data collected in our longitudinal database. Linaclotide responders were on medication for at least 12\u00a0months with documented effectiveness by the treating physician.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Thirty-one patients with SSc were treated with linaclotide. At the time of linaclotide initiation, 23 of these patients (74%) were classified as having severe GI disease, as defined by recurrent pseudo-obstruction, malabsorption, and\/or need for artificial nutrition (Medsger GI severity score\u2009\u2265\u20093). The majority of patients (90.3%; 28\/31) had a treatment response, while only three patients (9.7%) reported ineffectiveness or intolerable side effects. Low-dose linaclotide (\u2264\u2009145 mcg daily) was used in 18 patients and was effective in 94%. High-dose therapy (&gt;\u2009145 mcg daily) was effective in 11 of 13 patients (85%). Common side effects were diarrhea, cramping, or bloating (11\/31, 35%). Ineffectiveness, cost, and abdominal pain were complaints cited among those who discontinued therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Linaclotide is a well-tolerated and efficacious pro-secretory and pro-motility agent that can be used to manage refractory lower GI manifestations in SSc. We found that low-dose linaclotide is an effective option and may be better tolerated, though a subset of patients may require high dose regimens.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12876-021-01738-0","type":"journal-article","created":{"date-parts":[[2021,4,15]],"date-time":"2021-04-15T16:07:30Z","timestamp":1618502850000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Linaclotide for the treatment of refractory lower bowel manifestations of systemic sclerosis"],"prefix":"10.1186","volume":"21","author":[{"given":"Eric J.","family":"Dein","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fredrick M.","family":"Wigley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6461-8940","authenticated-orcid":false,"given":"Zsuzsanna H.","family":"McMahan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,4,15]]},"reference":[{"issue":"1","key":"1738_CR1","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1007\/s11926-011-0217-3","volume":"14","author":"G Gyger","year":"2012","unstructured":"Gyger G, Baron M. Gastrointestinal manifestations of SSc: recent progress in evaluation, pathogenesis, and management. Curr Rheumatol Rep. 2012;14(1):22\u20139.","journal-title":"Curr Rheumatol Rep"},{"key":"1738_CR2","doi-asserted-by":"publisher","first-page":"2437","DOI":"10.1002\/1529-0131(200011)43:11<2437::AID-ANR10>3.0.CO;2-U","volume":"43","author":"VD Steen","year":"2000","unstructured":"Steen VD, Medsger TA. Severe organ involvement in systemic sclerosis with diffuse scleroderma. Arthritis Rheum. 2000;43:2437\u201344.","journal-title":"Arthritis Rheum"},{"issue":"3","key":"1738_CR3","doi-asserted-by":"publisher","first-page":"247","DOI":"10.5301\/jsrd.5000214","volume":"1","author":"AB Shreiner","year":"2016","unstructured":"Shreiner AB, Murray C, Denton C, et al. Gastrointestinal manifestations of systemic sclerosis. 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The relationship between gastrointestinal transit, Medsger GI severity, and UCLA GIT 2.0 symptoms in patients with systemic sclerosis. Arthritis Care Res (Hoboken). 2020. Epub ahead of print.","DOI":"10.1002\/acr.24488"},{"issue":"1","key":"1738_CR17","doi-asserted-by":"publisher","first-page":"10322","DOI":"10.1038\/s41598-017-10835-8","volume":"7","author":"H Cao","year":"2017","unstructured":"Cao H, Liu X, An Y. Dysbiosis contributes to chronic constipation development via regulation of serotonin transporter in the intestine. 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The present study was approved by the Johns Hopkins Institutional Review Board.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"No personal health information is included requiring consent for publication.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"174"}}