{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T15:46:18Z","timestamp":1759938378429,"version":"3.37.3"},"reference-count":13,"publisher":"The Journal of Rheumatology","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Rheumatol"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Rituximab (RTX) is effective in the induction and maintenance of remission in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). However, uncertainty remains regarding the optimal maintenance dosing regimen. This work evaluates the relationship between variability in RTX dosing and pharmacological response in AAV.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A prospective cohort of patients with AAV (n = 28) with either granulomatosis with polyangiitis (n = 23) or microscopic polyangiitis (n = 5) receiving maintenance RTX therapy were followed in a single tertiary care academic medical center over a 2-year period. Patient demographics, RTX dosing information, and trough plasma RTX levels were collected along with laboratory measures of pharmacologic response, including B cell counts and ANCA titers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>RTX dosing information from 94 infusions with 59 trough samples were collected with a mean \u00b1 SD dose of 640 \u00b1 221 mg, dosing interval of 210 \u00b1 88 days, and trough plasma RTX concentration of 622 \u00b1 548 ng\/mL. RTX trough concentrations were associated with RTX dose (\u03c1 = 0.60, <jats:italic>P<\/jats:italic> &lt; 0.0001) and dosing interval (\u03c1 = \u20130.55, <jats:italic>P<\/jats:italic> &lt; 0.0001). RTX dosing intensity (mg\/d) was associated with RTX trough concentrations (\u03c1 = 0.57, <jats:italic>P<\/jats:italic> &lt; 0.0001). Higher dosing intensities were associated with undetectable B cell repopulation (<jats:italic>P<\/jats:italic> &lt; 0.0001), but not negative ANCA titers (<jats:italic>P<\/jats:italic> = 0.60). Stratification of dosing intensities based on the standard dosing regimen of 500 mg every 6 months (2.4\u20133.3 mg\/d) demonstrated that this regimen was associated with B cell repopulation in 8 of 17 doses (47%) compared to 0 of 23 doses (0%) with the high-dose regimen (&gt; 3.3 mg\/d; <jats:italic>P<\/jats:italic> &lt; 0.0001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>RTX maintenance dosing of 500 mg every 6 months may be inadequate to maintain B cell depletion in the treatment of AAV.<\/jats:p><\/jats:sec>","DOI":"10.3899\/jrheum.210361","type":"journal-article","created":{"date-parts":[[2021,8,1]],"date-time":"2021-08-01T12:25:18Z","timestamp":1627820718000},"page":"1718-1724","source":"Crossref","is-referenced-by-count":3,"title":["Dose-dependent Pharmacological Response to Rituximab in the Treatment of Antineutrophil Cytoplasmic Antibody-associated Vasculitis"],"prefix":"10.3899","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3903-6049","authenticated-orcid":false,"given":"Jason M.","family":"Springer","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3834-4672","authenticated-orcid":false,"given":"Ryan S.","family":"Funk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2262","published-online":{"date-parts":[[2021,8,1]]},"reference":[{"key":"2022062114101797000_48.11.1718.1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0909905"},{"key":"2022062114101797000_48.11.1718.2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1404231"},{"key":"2022062114101797000_48.11.1718.3","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2017-212878"},{"key":"2022062114101797000_48.11.1718.4","doi-asserted-by":"crossref","first-page":"179","DOI":"10.7326\/M19-3827","article-title":"Long-term rituximab use to maintain remission of antineutrophil cytoplasmic antibody-associated vasculitis: a randomized trial","volume":"173","author":"Charles","year":"2020","journal-title":"Ann Intern Med"},{"key":"2022062114101797000_48.11.1718.5","doi-asserted-by":"crossref","unstructured":"Smith R , Jayne D , Merkel P. A randomized, controlled trial of rituximab versus azathioprine after induction of remission with rituximab for patients with ANCA-associated vasculitis and relapsing disease [abstract]. Arthritis Rheum 2019;71 Suppl 10.","DOI":"10.1093\/ndt\/gfaa146.LB004"},{"key":"2022062114101797000_48.11.1718.6","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1093\/rheumatology\/kex484","article-title":"Pharmacokinetics of rituximab and clinical outcomes in patients with anti-neutrophil cytoplasmic antibody associated vasculitis","volume":"57","author":"Cornec","year":"2018","journal-title":"Rheumatology"},{"key":"2022062114101797000_48.11.1718.7","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1007\/s40262-019-00826-5","article-title":"Non-linear rituximab pharmacokinetics and complex relationship between rituximab concentrations and anti-neutrophil cytoplasmic antibodies (ANCA) in ANCA-associated vasculitis: the RAVE trial revisited","volume":"59","author":"Bensalem","year":"2020","journal-title":"Clin Pharmacokinet"},{"key":"2022062114101797000_48.11.1718.8","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1002\/acr2.11230","article-title":"Granulomatosis with polyangiitis and microscopic polyangiitis: a systematic review and meta-analysis of benefits and harms of common treatments","volume":"3","author":"Springer","year":"2021","journal-title":"ACR Open Rheumatol"},{"key":"2022062114101797000_48.11.1718.9","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0802311"},{"key":"2022062114101797000_48.11.1718.10","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2010.1658"},{"key":"2022062114101797000_48.11.1718.11","doi-asserted-by":"crossref","unstructured":"Springer JM , Funk RS. Defining a therapeutic window for rituximab maintenance therapy in ANCA-associated vasculitis: a longitudinal observational study. J Clin Rheumatol 2020 Dec 15 (Epub ahead of print).","DOI":"10.1097\/RHU.0000000000001688"},{"key":"2022062114101797000_48.11.1718.12","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1111\/bcp.14364","article-title":"Modelling of the relationship between infliximab exposure, faecal calprotectin and endoscopic remission in patients with Crohn\u2019s disease","volume":"87","author":"Dreesen","year":"2021","journal-title":"Br J Clin Pharmacol"},{"key":"2022062114101797000_48.11.1718.13","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1213277"}],"container-title":["The Journal of Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.3899\/jrheum.210361","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,21]],"date-time":"2022-06-21T21:13:21Z","timestamp":1655846001000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.jrheum.org\/lookup\/doi\/10.3899\/jrheum.210361"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,1]]},"references-count":13,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2021,11,1]]},"published-print":{"date-parts":[[2021,11]]}},"alternative-id":["10.3899\/jrheum.210361"],"URL":"https:\/\/doi.org\/10.3899\/jrheum.210361","relation":{},"ISSN":["0315-162X","1499-2752"],"issn-type":[{"type":"print","value":"0315-162X"},{"type":"electronic","value":"1499-2752"}],"subject":[],"published":{"date-parts":[[2021,8,1]]}}}