{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T13:12:25Z","timestamp":1789737145716,"version":"4.0.1"},"reference-count":31,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,7,29]],"date-time":"2020-07-29T00:00:00Z","timestamp":1595980800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>We assessed pharmacokinetics (PK), pharmacodynamics (PD), and PK\/PD relationships of interleukin\u20106 (IL\u20106), soluble IL\u20106 receptor, and C\u2010reactive protein (CRP) in serum, and absolute neutrophil count (ANC) in blood following single doses of subcutaneous sarilumab versus intravenous tocilizumab (NCT02097524) from patients with rheumatoid arthritis (RA) who are inadequate responders to methotrexate (MTX) and on a stable dose of MTX. Patients with RA randomized (1:1:1:1) to single\u2010dose sarilumab (150 or 200 mg subcutaneously) or tocilizumab (4 or 8\u00a0mg\/kg intravenously) were included (n = 101), and PK, PD, and PK\/PD relationships and safety were assessed over 6 weeks postdose. PK profiles for both drugs are described by parallel linear and nonlinear target\u2010mediated clearance pathways. PD markers showed similar onset of effect during the first week postdose, regardless of dose or route of administration. CRP and ANC decreased, with median postdose nadirs at 7\u201015 days for CRP and 3\u20105 days for ANC. Both drugs at low and high doses achieved the same nadir for ANC and a similar return toward baseline within 2 weeks postdose, suggesting a saturation of effect. Safety profiles of sarilumab and tocilizumab were generally similar. In conclusion, despite differences in PK, the onset of the decrease in CRP (efficacy) and ANC (safety) after a single dose were similar for subcutaneous sarilumab and intravenous tocilizumab. PD effects and safety were consistent with previous studies.<\/jats:p>","DOI":"10.1002\/jcph.1703","type":"journal-article","created":{"date-parts":[[2020,7,29]],"date-time":"2020-07-29T16:19:37Z","timestamp":1596039577000},"page":"90-104","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Pharmacokinetics and Pharmacodynamics of Subcutaneous Sarilumab and Intravenous Tocilizumab Following Single\u2010Dose Administration in Patients With Active Rheumatoid Arthritis on Stable Methotrexate"],"prefix":"10.1002","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0892-9079","authenticated-orcid":false,"given":"Anne J.","family":"Paccaly","sequence":"first","affiliation":[{"name":"Regeneron Pharmaceuticals, Inc.  Tarrytown New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavel","family":"Kovalenko","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals, Inc.  Tarrytown New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janie","family":"Parrino","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals, Inc.  Tarrytown New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"Boyapati","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals, Inc.  Tarrytown New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Xu","sequence":"additional","affiliation":[{"name":"Sanofi Genzyme  Bridgewater New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hubert","family":"van Hoogstraten","sequence":"additional","affiliation":[{"name":"Sanofi Genzyme  Bridgewater New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomonori","family":"Ishii","sequence":"additional","affiliation":[{"name":"Tohoku University Hospital  Sendai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John D.","family":"Davis","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals, Inc.  Tarrytown New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Thomas","family":"DiCioccio","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals, Inc.  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