{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T19:01:50Z","timestamp":1785870110079,"version":"3.56.0"},"reference-count":43,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T00:00:00Z","timestamp":1769644800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T00:00:00Z","timestamp":1769644800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Euro J of Neurology"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Many Parkinson's disease patients receiving oral levodopa\/carbidopa experience a troublesome wearing off effect. Higher doses to mitigate OFF\u2010time are limited by adverse effects occurring at peak dopamine levels, particularly dyskinesia. A novel strategy to reduce OFF\u2010time without increasing peak dopamine levels is the continuous subcutaneous infusion of levodopa\/carbidopa, or their prodrug equivalents foslevodopa\/foscarbidopa.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Assess whether subcutaneous infusion therapies safely reduce OFF\u2010time and improve quality of life scores compared to oral levodopa\/carbidopa.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We searched MEDLINE, Embase, CENTRAL and ICTRP up to 28th October 2024 for clinical trials comparing subcutaneous infusions of levodopa or foslevodopa to oral levodopa in Parkinson's disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Screening of 1114 records identified seven studies in which 725 patients received subcutaneous infusion regimens of levodopa\/carbidopa (ND0612) (407 patients) or foslevodopa\/foscarbidopa (318 patients). Moderate quality evidence indicated subcutaneous infusion reduced the daily duration of OFF\u2010time by 1.98\u2009h (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0004). Moderate quality evidence indicated improvements in health\u2010related quality of life score PDQ\u201039 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0003) and sleep score PDSS\u20102 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.02), but an increase in the rate of treatment\u2010emergent adverse events, mostly related to the infusion site (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.04).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Subcutaneous infusion therapies produce a clinically and statistically significant reduction in the duration of OFF\u2010time experienced by patients with Parkinson's disease, compared to oral levodopa\/carbidopa. Patient experience is improved by a statistically, but not clinically, significant degree. There are increased adverse events, mostly related to the infusion site. Overall, subcutaneous infusion regimens could provide a meaningful alternative for Parkinson's disease patients who experience severe motor fluctuations with existing levodopa formulations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/ene.70506","type":"journal-article","created":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T13:39:32Z","timestamp":1769693972000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Subcutaneous Levodopa in Parkinson's Disease: A Systematic Review and Meta\u2010Analysis"],"prefix":"10.1111","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-9030-1198","authenticated-orcid":false,"given":"Matthew","family":"Burton","sequence":"first","affiliation":[{"name":"University of Oxford Medical Sciences Division  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9519-7025","authenticated-orcid":false,"given":"Duncan","family":"Marsden","sequence":"additional","affiliation":[{"name":"University of Oxford Medical Sciences Division  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8685-8811","authenticated-orcid":false,"given":"Dhruv","family":"Harish","sequence":"additional","affiliation":[{"name":"University of Oxford Medical Sciences Division  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0867-0570","authenticated-orcid":false,"given":"Peter","family":"Morris","sequence":"additional","affiliation":[{"name":"University of Oxford Medical Sciences Division  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl","family":"Heneghan","sequence":"additional","affiliation":[{"name":"Centre for Evidence\u2010Based Medicine University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ailsa","family":"Butler","sequence":"additional","affiliation":[{"name":"Centre for Evidence\u2010Based Medicine University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Nunan","sequence":"additional","affiliation":[{"name":"Centre for Evidence\u2010Based Medicine University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,29]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.14108"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ncl.2008.05.003"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2025.107317"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0225723"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.1090"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1159\/000300647"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells11233736"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.25.12.1144"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12325-021-01747-1"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.3233\/JPD-212813"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.26073"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2022.1036068"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/mdc3.14138"},{"key":"e_1_2_11_15_1","unstructured":"J. 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