{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T02:36:13Z","timestamp":1782700573827,"version":"3.54.5"},"reference-count":72,"publisher":"BMJ","issue":"9","license":[{"start":{"date-parts":[[2020,9,17]],"date-time":"2020-09-17T00:00:00Z","timestamp":1600300800000},"content-version":"unspecified","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008272","name":"Novartis Pharmaceuticals Corp.","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100008272","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2020,7,14]]},"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Treatment options for preventing vaso-occlusive crises (VOC) among patients with sickle cell disease (SCD) are limited, especially if hydroxyurea treatment has failed or is contraindicated. A systematic literature review (SLR) and network meta-analysis (NMA) were conducted to evaluate the efficacy and safety of crizanlizumab for older adolescent and adult (\u226516 years old) SCD patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The SLR included randomised controlled trials (RCTs) and uncontrolled studies. Bayesian NMA of VOC, all-cause hospitalisation days and adverse events were conducted.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The SLR identified 51 studies and 9 RCTs on 14 treatments that met the NMA inclusion criteria. The NMA found that crizanlizumab 5.0\u2009mg\/kg was associated with a reduction in VOC (HR 0.55, 95% credible interval (0.43, 0.69); Bayesian probability of superiority &gt;0.99), all-cause hospitalisation days (0.58 (0.50, 0.68); &gt;0.99) and no evidence of difference on adverse events (0.91 (0.59, 1.43) 0.66) or serious adverse events (0.93 (0.47, 1.87); 0.59) compared with placebo. The HR for reduction in VOC for crizanlizumab relative to L-glutamine was (0.67 (0.50, 0.88); &gt;0.99). These results were sensitive to assumptions regarding whether patient age is an effect modifier.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This NMA provides preliminary evidence comparing the efficacy of crizanlizumab with other treatments for VOC prevention.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2019-034147","type":"journal-article","created":{"date-parts":[[2020,9,18]],"date-time":"2020-09-18T04:40:12Z","timestamp":1600404012000},"page":"e034147","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":9,"title":["Crizanlizumab and comparators for adults with sickle cell disease: a systematic review and network meta-analysis"],"prefix":"10.1136","volume":"10","clinical-trial-number":[{"clinical-trial-number":"nct02482298","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct02482298","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Howard","family":"Thom","sequence":"first","affiliation":[{"name":"Bristol Medical School, University of Bristol, Bristol, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeroen","family":"Jansen","sequence":"additional","affiliation":[{"name":"Health Economics, PRECISIONheor, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Shafrin","sequence":"additional","affiliation":[{"name":"Health Economics, PRECISIONheor, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6339-149X","authenticated-orcid":false,"given":"Lauren","family":"Zhao","sequence":"additional","affiliation":[{"name":"Health Economics, PRECISIONheor, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Joseph","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals Corp, East Hanover, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hung-Yuan","family":"Cheng","sequence":"additional","affiliation":[{"name":"Bristol Medical School, University of Bristol, Bristol, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Subhajit","family":"Gupta","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals Corp, East Hanover, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nirmish","family":"Shah","sequence":"additional","affiliation":[{"name":"Department of Medicine, Duke University, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2020,9,17]]},"reference":[{"key":"2026062608022071000_10.9.e034147.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amepre.2009.12.022"},{"key":"2026062608022071000_10.9.e034147.2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-05-498311"},{"key":"2026062608022071000_10.9.e034147.3","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-09-618538"},{"key":"2026062608022071000_10.9.e034147.4","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.110.211615"},{"key":"2026062608022071000_10.9.e034147.5","doi-asserted-by":"publisher","DOI":"10.3109\/09537104.2013.770136"},{"key":"2026062608022071000_10.9.e034147.6","doi-asserted-by":"publisher","DOI":"10.1126\/science.1256478"},{"key":"2026062608022071000_10.9.e034147.7","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-02-0626"},{"key":"2026062608022071000_10.9.e034147.8","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V98.6.1955"},{"key":"2026062608022071000_10.9.e034147.9","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-01-078204"},{"key":"2026062608022071000_10.9.e034147.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.chest.2015.12.016"},{"key":"2026062608022071000_10.9.e034147.11","unstructured":"Lanzkron S . 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