{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T14:50:23Z","timestamp":1747147823811,"version":"3.40.5"},"reference-count":32,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,9,27]],"date-time":"2024-09-27T00:00:00Z","timestamp":1727395200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:p>The CRISPR\u2010based gene editing therapy exagamglogene autotemcel (exa\u2010cel) recently received FDA approval for patients with severe sickle cell disease (SCD). The approval was based on a phase III trial (CLIMB SCD 121), which showed 97% efficacy of this treatment in eliminating vaso occlusive crises (VOCs) for 12 consecutive months. To help contextualize results from this trial, we aimed to investigate the proportion of patients with severe SCD who remain VOC\u2010free for a 1\u2010year period in routine clinical care. Using Medicaid claims data (2000\u20132018), we identified a cohort of patients, 12\u201335\u2009years old with severe SCD, defined by \u2265\u20092 VOCs per year for 2 consecutive years, who met other exa\u2010cel trial inclusion criteria to mimic a trial\u2010like population. A VOC was identified using ICD diagnosis codes during hospitalization and ER visits. The primary outcome was the proportion of patients with no VOCs during a 1\u2010year follow\u2010up. A total of 7,425 patients with severe SCD [mean (SD) age: 20.5 (6.0) years, 54.6% females, 84% African Americans], had a mean of 5.2 VOCs, 5.1 ER visits and 3.5 hospitalizations per year during the baseline period. The proportion of patients with no VOCs during the 1\u2010year follow\u2010up was 7.7% (95% confidence interval: 7.1%\u20138.3%). In conclusion, less than one in 12 patients with severe SCD achieved VOC\u2010free status within 1\u2009year in routine clinical care. These findings suggest that the high efficacy observed for exa\u2010cel in the trial, if replicated in routine clinical care, could translate into a significant public health impact.<\/jats:p>","DOI":"10.1002\/cpt.3449","type":"journal-article","created":{"date-parts":[[2024,9,27]],"date-time":"2024-09-27T08:36:42Z","timestamp":1727426202000},"page":"1572-1579","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Infrequent Resolution of Vaso\u2010Occlusive Crises in Routine Clinical Care Among Patients Mimicking the Exa\u2010Cel Trial Population: A Cohort Study of Medicaid Enrollees"],"prefix":"10.1002","volume":"116","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6684-2337","authenticated-orcid":false,"given":"Mufaddal","family":"Mahesri","sequence":"first","affiliation":[{"name":"Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine Brigham and Women's Hospital &amp; Harvard Medical School  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3437-097X","authenticated-orcid":false,"given":"Su Been","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine Brigham and Women's Hospital &amp; Harvard Medical School  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raisa","family":"Levin","sequence":"additional","affiliation":[{"name":"Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine Brigham and Women's Hospital &amp; Harvard Medical School  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suzan","family":"Imren","sequence":"additional","affiliation":[{"name":"Vertex Pharmaceuticals Inc.  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lanju","family":"Zhang","sequence":"additional","affiliation":[{"name":"Vertex Pharmaceuticals Inc.  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9463-6306","authenticated-orcid":false,"given":"Timothy","family":"Beukelman","sequence":"additional","affiliation":[{"name":"Vertex Pharmaceuticals Inc.  Boston Massachusetts USA"},{"name":"Epi Excellence LLC  Garnet Valley Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1801-1168","authenticated-orcid":false,"given":"Lina","family":"Titievsky","sequence":"additional","affiliation":[{"name":"Vertex Pharmaceuticals Inc.  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0299-7273","authenticated-orcid":false,"given":"Rishi J.","family":"Desai","sequence":"additional","affiliation":[{"name":"Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine Brigham and Women's Hospital &amp; Harvard Medical School  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,9,27]]},"reference":[{"volume-title":"Pathophysiology of Blood Disorders","year":"2011","author":"Bunn H.F.","key":"e_1_2_10_1_1"},{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amepre.2009.12.022"},{"key":"e_1_2_10_3_1","unstructured":"CDC.Sickle cell disease data & statistics<http:\/\/www.cdc.gov\/ncbddd\/sicklecell\/data.html> (2016)."},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2010.378"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2018.10"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathmechdis-012418-012838"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-03-079665"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0027-9684(15)30725-2"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199505183322001"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(11)60355-3"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mayocp.2018.08.001"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/asheducation-2013.1.370"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejh.13546"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2019.11419"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2117175"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2029392"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2031054"},{"key":"e_1_2_10_18_1","unstructured":"Exagamglogene autotemcel (exa\u2010cel) for the treatment of sickle cell disease in patients 12\u2009years and older with recurrent vaso\u2010occlusive crises BLA125787. Sponsor briefing document<https:\/\/www.fda.gov\/media\/173415\/download>."},{"key":"e_1_2_10_19_1","unstructured":"FDA press release. FDA Approves First Gene Therapies to Treat Patients with Sickle Cell Disease<https:\/\/www.fda.gov\/news\u2010events\/press\u2010announcements\/fda\u2010approves\u2010first\u2010gene\u2010therapies\u2010treat\u2010patients\u2010sickle\u2010cell\u2010disease>."},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2309676"},{"volume-title":"Healthcare Cost and Utilization Project (HCUP) Statistical Briefs [Internet]","year":"2006","author":"Fingar K.R.","key":"e_1_2_10_21_1"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2012.128"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.22792"},{"key":"e_1_2_10_24_1","unstructured":"<https:\/\/www.cms.gov\/Research\u2010Statistics\u2010Data\u2010and\u2010Systems\/Computer\u2010Data\u2010and\u2010Systems\/MedicaidDataSourcesGenInfo\/MAXPC>."},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199505183322001"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1715971"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1903212"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1611770"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1177\/003335491312800206"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1182\/asheducation-2017.1.435"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00277-020-04233-w"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0214355"}],"container-title":["Clinical Pharmacology &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpt.3449","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,15]],"date-time":"2024-11-15T06:23:57Z","timestamp":1731651837000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1002\/cpt.3449"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,27]]},"references-count":32,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2024,12]]}},"alternative-id":["10.1002\/cpt.3449"],"URL":"https:\/\/doi.org\/10.1002\/cpt.3449","archive":["Portico"],"relation":{},"ISSN":["0009-9236","1532-6535"],"issn-type":[{"type":"print","value":"0009-9236"},{"type":"electronic","value":"1532-6535"}],"subject":[],"published":{"date-parts":[[2024,9,27]]},"assertion":[{"value":"2024-05-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-27","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}